siRNA Therapies

In Akhtar and Benter’s 2007 paper there is a sense of an improved therapy, yet today we still are waiting for those new therapeutics. This feeling is summed up in Aldridge’s 2011 article; “RNA interference – still the great white hope?“.

From 2007 we have this enticing table of currently running clinical or preclinical trials:

The question is; what happened to them?

Okay readers, onto the comments for an update from the Toxicogenomics class…

82 thoughts on “siRNA Therapies

  1. 2011 Update for RSV Lung Infection:

    Respiratory synical virus, also known as RSV, is the cause of infection in the lungs and breathing passageways of many young children. RSV can also be found in adults where its symptoms show up as just the common cold, or in children, where it poses much more serious health effects such as bronchitis or pnemonia.RSV is very contagious especially in young children and can be spread through salvia, as well as salvia droplets produced when an affected patient coughs or sneezes. A few years ago, Alnylam developed an siRNA product called ALN-RSV01 to treat RSV. Since then, patients treated with the ALN-RSV01 siRNA product have shown decreased rates of infection, as well as in increase in the number of people who did not contract the virus. In addition to these positive results, ALN-RSV01 seems to be safe and well tolerated by patients. To further test out the ALN-RSV01’s ability to treat RSV, a test known as “GEMINI” was conducted. During Gemini, patients were given an ALN-RSV01 pill, or a placebo for five days in a row. The study found a 38.7% reduction rate of infection in patients that received that ALN-RSV01 pill, as well as a 95% increase in the number of patients who were completely free of the virus, in comparison with those who received the placebo. Clearly, the results from the GEMINI study showed that ALN-RSV01 ‘demonstrates clear anti-viral activity’, and is more than capable of treating RSV. These findings will help combat RSV for many generations to come. ALN-RSV01 is the first new drug in years found to treat RSV, and perhaps its biggest contribution to medicine is one found in Alnylam’s announcement for a conference call, stating that ALN-RSV01’s data supports “continued development of the RNAi therapeutic for the treatment of RSV infection, a major unmet medical need”.

    • I think your response on RSV, respiratory synical virus, is very interesting. It’s shocking how RSV can be found in symptoms of common cold since not many people know it can be found in common cold. I agree that it can pose much more serious health effects in children than adults. I think since RSV is very contagious especially in young children and can be spread through salvia people should be very careful not to let their children spread such dieses because it can be unsafe for others. If the patients can be treated with the ALN-RSV01 siRNA product which has shown to decreased rates of infection, this treatment can be very good thing for the people with RSV. I think it’s very sad that RSV increase in the number of people who did not contract the virus. It’s great that ALN-RSV01 seems to be safe and well tolerated by patients. I think ALN-RSV01’s ability to treat RSV can be a great help for many people.

    • This one of the ways that the companies testing the siRNAs to find cures for various diseases. The strides that have been making in curing diseases such is RSV. It is probably the hardest to watch a child suffer through a disease and even harder to watch them go through treatment such as cancer. What is nice about this drug is the fact that it is a pill so it is very user friendly in many ways and young kids who make a fuss about medicine can secretly be given this pill (if it is not too big). What is interesting is that no side effects have been mentioned in taking the pill. That would be very interesting to see.

    • Respiratory syncytial virus (RSV) causes morbidity in infants, young children, and the elderly worldwide. Up to now, there is still no effective vaccine, and antiviral drugs to control infection are limited. If RNAi therapeutic for the treatment of RSV infection is well developed ultimately, it definitely would be great news.

    • I also did my post on RSV and The thing I find really scary about this virus is that it doesn’t really have many sign that jump out at you to make you think that it maybe RSV so you might go days with this virus, just thinking its a cold or the flu, but later on when this virus manifests to phenomena or something potentially deadly it maybe too late.

      • Like the people stated above I would hate to see a child (or anyone) die of RSV. Shame it sort of disguises itself as a cold, but glad to see that there is a drug which means help for this disease.

    • Drugs like ALN-RSV01 can help save a lot of people’s lives especially infants. Many of them died very young which made their parents heartbroken. Hopefully, very soon, the RSV infection would be nothing but just a common cold; a disease that can be easily cured and prevented.

  2. Liver cancer is cancer that forms in the tissues of the liver. Worldwide, liver cancer is the most common solid organ tumor, with more than 600,000 people diagnosed each year. The incidence of primary liver cancer is increasing due to underlying liver disease such as hepatitis infection and alcoholism. The overall five-year relative survival rate from liver cancer is about 10 percent, making it the cancer with the second poorest five-year survival rate. Liver cancer may be treated with surgery, radiation therapy or chemotherapy. The liver is also a common site for metastasis in other types of cancer, also known as secondary liver cancer. More than 500,000 people worldwide are diagnosed with secondary liver cancer each year; up to 50 percent of liver metastases are of colorectal cancer origin, while the remainder metastasizes from a wide variety of primary cancer sites including breast and kidney. Cancer of the liver, including primary (hepatocellular carcinoma) and secondary (metastatic) tumors, represent a significant unmet medical need. We are developing a therapeutic for solid tumors involving the liver that is comprised of lipid particle-formulated short interfering RNAs (siRNAs) targeting VEGF and the mitotic kinesin, KSP. For each target, potent siRNA duplexes were selected following extensive screening in tissue culture cells. Efficacy was demonstrated in a mouse liver tumor model. To assess efficacy in vivo, a stable nucleic acid lipid particle (SNALP) formulation was developed based on similar formulations previously shown to silence liver-expressed genes via systemic administration in multiple species. A SNALP-formulated combination of the KSP and VEGF siRNAs (referred to as ALN-VSP01) was tested in an orthotopic liver tumor model in which human hepatoma cells (Hep3B) are implanted directly into the livers of immunocompromised mice. Intravenous administration of ALN-VSP01 leads to dose-dependent inhibition of both KSP and VEGF expression in established liver tumors. This was accompanied by the formation of numerous aberrant mitotic figures (“monoasters”) in tumor cells indicative of the pharmacologic inhibition of KSP. In addition, tumor growth was significantly inhibited by a course of ALN-VSP01 treatment, and ALN-VSP01 treatment provided a clear survival benefit even when treatment was initiated in animals with a significant tumor burden. As a control, a SNALP-formulated siRNA targeting Luciferase was administered and shown to have no effect in these studies. Systemic administration of ALN-VSP01 exhibited clear efficacy in a mouse orthotopic liver tumor model. ALN-VSP01, is comprised of two small interfering RNAs, or siRNAs, the molecules that mediate RNAi. Each siRNA targets a distinct and well-validated gene in the growth and proliferation of tumors: VEGF, a key mediator of tumor angiogenesis; and KSP, a protein required for cell division that, when inhibited, leads to cell arrest and cell death in dividing cells. ALN-VSP01 is formulated using Alnylam’s novel liposomal formulation technology, which has been used to achieve delivery of siRNAs to cells of the liver and efficient silencing of genes expressed in that organ. Liposomal delivery can also be optimized for delivery to other organs and tumor types, such that ALN-VSP01 may ultimately have potential for a range of solid tumors. Alnylam’s collaborator, Inex Pharmaceuticals Corporation, is manufacturing the lipid-based formulation as the company prepares for pre-IND toxicology studies with ALN-VSP01.

    • I liked your response on liver cancer and this kind of diseases that forms in the tissues of the liver is very serious. It’s a worldwide issue since liver cancer is the most common solid organ tumor and more than 600,000 people diagnosed each year. I think ALN-VSP01 can help solve this problem since it’s a novel liposomal formulation technology. It’s great that this technology has been used to achieve delivery of siRNAs to cells of the liver and efficient silencing of genes expressed in that organ. I agree that this liposomal delivery can also be optimized for delivery to other organs and tumor types, which can be very beneficial to people with cancers. This type of technology may ultimately be used to cure primary liver cancer since it is increasing due to underlying liver disease. I think this technology can be very beneficial to many people with liver cancer, who are looking for a cure.

    • Liver cancer is one of the many cancers that people have and its treatments are very painful. It is due to the patient’s bad habits such as drinking too much alcohol but sometimes unfortunately it’s a hereditary disease. Maybe in the future, as medical technology advance and medication are more effective, this illness can be cured.

  3. Liver cancer is one of the most common cancers in the world. There are two types, primary liver cancer and secondary liver cancer. Primary liver cancer also known as heptacellular carcinoma affects the liver only (or mostly only). The cancer is caused mostly by cirrhosis (scaring of the liver) often caused by alcohol abuse, autoimmune disease of the liver, long term inflammation of the liver, Hepatitis B/C and even too much iron in the body. The Secondary Liver cancer starts somewhere else in the body and eventually goes to the liver. It is also called metastatic liver cancer.
    In 2007, the company Alnylam was trying to use the siRNA, ALN-RSV01 to treat Liver cancer. At the time, the treatment was still in the preclinical stage. 3 years later in 2010, they have gone through Phase I of the testing in treating Liver Cancer in patients and submitted results to the Chemotherapy Foundation Symposium. The ALN-VSP is targeted toward two main genes that promote liver cancer: kinesin spindle proten (KSP) and vascular endothelial growth factor (VEGF). KSP is involved in cancer propagation (makes the cancer grow and spread) and the VEGF allows new blood vessels to grow from the tumors to “feed” them.
    The drug is made by lipid nanoparticle (stable nucleic acid-lipid particle) and in the preclinical studies, ALN-RSV01 showed signs that it could turn off the KSP and VEGF genes and essentially stop the growth of the cancer. In animal studies it showed that the tumor had decreased in size and decreased the number of tumors found in the liver. In the first test phase in 2009, the initial 28 patients showed well toleration of the treatment even after 6 doses. The initial doses were very small ranging from 0.1 to 1.25 mg/kg and the number of doses per patient is in the range between 2 to 13 doses each. Those who have received a large number of doses at a higher dose have shown stability in improved and have been asked to continue the treatment.

  4. Age-related macular degeneration (AMD) , an eye disease that destroys central vision by damaging the macula, is the leading cause of visual impairment affecting more than 1.5 million adults over the age of 50 in the United States. The macula is part of the retina which lines most of the inside of the eye. While nerve cells in the retina detect light and send signals to the brain about what the eye sees, macula provides the clear, sharp, central vision that is used to focus on objects that are in front of the eye. AMD occurs with increasing frequency as people age.
    In 2006, the company Sirna Therapeutics presented the experiment of siRNA which directed against VEGFR1 mRNA for AMD. They announced that Sirna-027 appeared to be safe and well tolerated at doses tested to date, with no systemic or local adverse events related to the drug. No dose-limiting toxicity has been observed; thus the maximum tolerated dose has not been established. Their data demonstrated that fourteen patients have each received a single intravitreal dose of Sirna-027 ranging from 100 to 800 micrograms. And all patients have experienced visual acuity stabilization during their trial participation. They thought that siRNAs may emerge as an important and novel therapeutic modality for AMD.
    siRNA Therapeutics company developed siRNA-027 to target VEGF receptor 1 (VEGFR1). VEGF receptor 2 (VEGFR2) is thought to be the main receptor that drives pathological angiogenesis. The role of the VEGFR1 is not completely understood, but some evidence supports that VEGFR1 may function as a decoy receptor, meaning that it binds up VEGFA so that it does not have access to VEGFR2. A phase 1 and 2 dose-escalation trial was performed at the Wilmer Eye Institute and Cleveland Clinic. The trial suggested that the agent was efficacious. However, A further phase 2 trial failed to meet an efficacy hurdle though it had no safety issues.

    • Almost none of the siRNA experiments on AMD lead to no safety concerns. It was the matter of efficacy. Another siRNA experiment that was done was with the use of a siRNA called RTP801i-14.

  5. Age-related macular degeneration, also known as AMD is a disease that is associated with aging and gradually destroys the central vision. Our central vision is used for seeing objects sharp and clearly, tasks accomplished with our central vision can include seeing the sharpness and objects while driving and reading. Specifically this disease destroys the macula, which is located in the center of the retina of the eye. It causes no pain, and in some cases it will effect people so slowly that they may not even notice the changing of their vision, however, in other cases the disease may occur very rapidly and cause loss of vision in both eyes.
    Acuity Pharmaceuticals was the first company to have a human clinical trial with siRNA in 2004 to treat AMD. In the “wet” form of AMD the siRNA (Cand5) was targeting the disease in order to prevent the overgrowth of new blood vessels. Wet AMD occurs when abnormal blood vessels form behind the retina and begin to grow under the macula. These new blood vessels are very delicate and most likely leak blood and other fluids. Therefore the blood and fluids raise the macula above the normal level and begin to almost instantly cause damage. This treatment therefore stopped the production of these new blood vessels, lowering the level of the macula back to its normal limits and in hopes ceasing any further damage.
    This treatment has now reached it’s phase II clinical evaluation, showing the preliminary result that there can be and are dose-related benefits in treatment of wet AMD with nearer vision and lesion sizes. However as for now, Opko Halts have attempted a phase III evaluation in 2009 and the developer claimed that therapy was deemed “unlikely” to meet its primary endpoints that were originally hoped for.

    information of the phase III attempted evaluation:

    • J’nelle,
      I thought this was easy to understand and a well written analysis of AMD which seems to be very popular with everyone. and i liked how in your ending you left good enough room for uncertainty although the research has reached far enough for an attempt at phase III.

      • This post was very interesting in my opinion. I felt it was very informative and well written. You touched on every points that that needed to be made. I have come away more aware of the disease and interested in knowing more that there is to find out.

  6. Wet age-related macular degeneration (AMD) is the number one cause of irreversible vision loss. It is associated with aging and the gradual loss of sharp and central vision. This occurs when the abnormal blood vessels behind the retina start to grow under the macula which can leak blood and flood. This can raise the macula and cause damage to it.

    Clinical compound bevasiranib sodium, formerly known as Cand5, appeared safe and showed clinical evidence of efficacy. Bevasiranib is a small interfering RNA (siRNA) designed to turn off the gene that produces vascular epithelial growth factor (VEGF), the growth factor believed largely responsible for wet age-related macular degeneration. VEGF has been shown to be the central stimulus in the development of wet AMD. The small interfering mRNA shut off the gene that encodes for the production of VEFG-A, inhibiting choroidal neovascularization.

    The Acuity Pharmaceuticals had phase I studies of the drug and found out that the drug is safe and well tolerated. They also found out that the drug did not escape into the systemic circulation. During phase II trials, they had a randomized study (C.A.R.E.), a double-masked trial that had 129 patients with AMD. They received three dose levels of Cand5 over six months. The results showed that the lowest dose (0.2mg) lasted on average for 153 days before they needed another injection. The higher dose lasted even longer. In their phase III trial (CARBON), they plan to pre-treat patient with Lucentis (currently used drug for AMD) and then treat with Cand5 versus Lucentis alone.

  7. There are many therapeutic application of RNA interference (RNAi) and several compounds are now approaching clinical trials. Amongst the first to reach this hurdle is sirna-027, a small interfering RNA targeting vascular endothelial growth factor receptor 1, which is a treatment for age-related macular degeneration (AMD). AMD is the most common cause of blindness which results from damage to the macula, the part of the retina responsible for fine vision, though the periphery remains unaffected and so total blindness does not result. There are two clinically distinct forms: dry AMD and wet AMD. RNA usually acts as a messenger within the cell, carrying instructions from DNA within the cell’s nucleus out to locations within the cell where the genetic instructions are used to build proteins. Interfering RNA intercepts and destroys the messenger RNA for specific proteins by a process known as gene silencing. In this study, the gene for a key vascular endothelial growth factor (VEGF) receptor was silenced, and patients with wet AMD showed improvement.

    There is no current cure for AMD, although laser surgery or photodynamic therapy may be used to slow the progression of wet AMD. This new study found that a single intravitreal dose of sirna-027 was well tolerated. Sirna-027 is targeted to VEGFR-1, an endothelial growth factor receptor that stimulates the growth of new blood vessels, aiming to reduce the pathological angiogenesis associated with AMD. Application of sirna-027 is by direct injection into the eye, thereby negating many problems associated with delivery and stability in the body. VEGF has two cell surface receptors and both of which are tyrosine kinases: VEGF receptor 1 (VEGFR-1) and VEGF receptor 2 (VEGFR-2). These receptors are potential targets for treatment of neovascular AMD, not only because VEGF inhibition is so successful, but also because inhibition of individual receptors may allow particular aspects of the angiogenic process to be modulated and inhibition of a receptor with multiple ligands may have a greater effect than simply inhibiting the action of a single ligand.

    Sirna-027 is a chemically modified small interfering RNA (siRNA) molecule that targets a conserved region of human VEGFR-1. These siRNA molecules induce gene silencing by binding to complementary target RNA molecules in association with the nucleolytic cytoplasmic protein complex known as the RNA induced silencing complex. Based on the preclinical activity and tolerability of sirna-027, the current phase I study was conducted. The study was designed to demonstrate the safety and tolerability of single ascending intravitreal doses of Sirna-027 and to evaluate the proof of principle biological activity of Sirna-027 in patients with CNV secondary to AMD. In this study sirna-027 has been chemically modified and has shown a significantly improved pharmacokinetic profile in pre-clinical studies compared to unmodified siRNAs. Phase I clinical findings have so far proved positive. Of 14 patients with the blindness-causing wet AMD, deterioration in visual acuity has been halted and a dose-dependent improvement in reading tests observed. Additionally, thickening of the retina has been reduced in six of seven patients examined using optical coherence tomography.

    • References

      Kaiser PK, Symons RC, Shah SM, Quinlan EJ, Tabandeh H, Do DV, Reisen G, Lockridge JA, Short B, Guerciolini R, Nguyen QD; Sirna-027 Study Investigators (2010). RNAi-based treatment for neovascular age-related macular degeneration by Sirna-027. Cole Eye Institute, Cleveland Clinic, Ohio, USA.
      PMID: 20609706

  8. Age-related Macular Degeneration (AMD) is a disease that destroys a person’s central vision gradually as a person ages. Central vision allows a person to see objects clearly in fine details, and to perform daily activities such as: reading, driving. Central vision also allows a person to interpret colors and shapes of the object that is being viewed. In order for a person’s central vision to work properly, macula, which is part of the retina, must be functional. AMD becomes the main cause of blindness in people older than 60 years in the US. The main cause of AMD is a person’s age. Studies shows that people over 60 years old have a higher risk of getting AMD. Other factors including: smoking, obesity, race and family history and gender. But overall, a healthy life style can reduce the risk of getting AMD. There are two forms of AMD: dry AMD (early stage) and wet AMD (the late stage). They symptom of dry AMD are blurring central vision and the presence of drusen. Drusen is the small, round, white-yellow deposits at the retina. During advanced dry AMD stage, the blurred spot that is caused by the breakdown of light-sensitive cells and tissues in retina will affect the central vision. Eventually, the condition can get worse when the blurred spot gets bigger and darker. Dry AMD accounts for 85%-90% of all cases. The symptoms of wet AMD are the growth of abnormal blood vessels under the retina. These blood vessels destroy the central vision. The risk of losing sight is much more quicker and greater than dry AMD. In 2005, Sirna Therapeutics, Inc. had completed the phase I clinical trial for Sirna-027. Sirna-027 targets the Vascular Endothelial Growth Factor Receptor-1 (VEGFR-1) to reduce the pathologic angiogenesis mediated by VEGF and placental growth factor PIGF. Data shows that Sirna’s AMD program is safe and well tolerated. After the single dose of Sirna-027, 25% of patients showed visual acuity improvement after 8 weeks. This treatment had entered phase II clinical trial in 2006.

    • You did a good job of writing and fully explaining everything without getting to technical and wordy which made it easy to read.

  9. Age-related macular degeneration (AMD) is a disease associated with aging that gradually destroys sharp, central vision. Central vision is needed for seeing objects clearly and for common daily tasks such as reading and driving. This disease, AMD affects the macula, the part of the eye that allows us to see fine detail.
    In some cases, AMD advances so slowly that people notice little change in their vision. In others, the disease progresses faster and may lead to a loss of vision in both eyes. AMD is a leading cause of vision loss in Americans 60 years of age and older.
    Sirna Therapeutics, Inc., whis operates as a subsidiary of Merck, is a leading RNAi-based therapeutics company whoreported the final results from its recently completed Phase 1 trial for Sirna-027, a new therapeutic for AMD. In a study of 26 patients, single ascending doses of Sirna-027 were safe and well tolerated, and all 26 patients (100%) showed visual sharpness stabilization eight weeks after a single injection. In addition, at the same time point, five of 26 patients (19%) experienced clinically significant improvement in visual sharpness, indicated by an increase of at least three lines on an eye chart.
    Three months after a single injection, 24 of 26 patients (92%) showed visual sharpness stabilization, with four of 26 patients (15%) experiencing clinically significant improvement in visual sharpness; only two of 26 patients (8%) experienced a reduction in visual sharpness of three lines or more. This shows that this RNAi can actually work
    In September 2005, Sirna and Allergan, Inc., a global leader in eye care, established a strategic alliance in eye diseases which includes Sirna-027 for AMD. Under the terms of the Agreement, Allergan assumed all developmental and commercialization costs for Sirna-027. Sirna and Allergan expect to initiate the Phase 2 trial during the second half of 2006.

    • Nancy your claim that siRNA was very sucesful based on your statistical data you provided. SiRNA – 27 in fact has indeed been successful. The data you provided was very accurate and there were a lot of supporting details to support your claim.

  10. Age-Related Macular Degeneration (AMD) is the leading cause of vision loss or blindness among Americans aged 65 years or older. It involves the degeneration of the macula, which is the part of the retina responsible for sharp vision needed to drive, sign checks, read, and even differentiate between colors. There are two types of AMD: Wet Macular Degeneration (neovascular) and Dry Macular Degeneration (non-neovascular). Wet Macular Degeneration is causes more serious vision loss because new blood vessels grow in areas where there are not supposed to grow. In this case blood vessels grow in the macula. Dry Macular Degeneration is not as serious but still leads to blindness. It involves the accumulation of spots, believed to be debris from deteriorating tissue. There are no FDA approved treatments for Dry Macular Degeneration but, a few clinical trials exist. In May 2009, the Allergen gene company stopped its development of its siRNA based Wet AMD treatment after the drug failed to meet an “effective endpoint” in a Phase II study. The siRNA was originally owned by the Sirna Therapeutic Company and was originally called ‘Sirna-027’ until Allergen bought the siRNA up front for 5 million dollars and called it AGN-745. Sirna-027/AGN-745 is a chemically modified siRNA targeting vascular endothelial growth factor receptors. The siRNA was to be administered intravenously once a month. The study compared results with the antibiotic drug Lucentis, also administered intravenously. There were several media devices claiming that this siRNA would be the second type of siRNA to be used in human clinical trials but unfortunately, there was insufficient experimentation for the advancement of this research.

    • Your post was very informative and interesting, your post was probably the only one that talked about both types of AMD and made it clear to me what they were. It crazy how they still have not had a major breakthrough in a while and are still only in trails with the cure for it, hopefully by the time we are that age there might a treatment for AMD.

    • I also wrote about AMD, but I think I researched it because I had read your’s first. It was very well written in that it was very informative, yet organized, making it easier to both read and understand. Also, I like how you concluded that there wasn’t enough experimentation to continue this research. I hope that they would continue researching on this because of the cure of AMD may be present through siRNA! Also, because there was no safety concerns using siRNA for AMD, it makes it a more possible candidate to be helpful for those with have AMD.

  11. Age-related macular degeneration is a disease which usually causes visual impairment in adults older than 50. In the most severe case of this disease, called the wet form, blood vessels grow abnormally behind the retina of the eye (which may even cause retinal detachment). The blood vessels that build up cause blood and protein leakage which can ultimately lead to irreversible harm to photoreceptors in the eye, resulting in rapid vision loss.

    A small interfering RNA called siRNA-027 targets vascular endothelial growth factor receptor-1 which inhibits the RNA coded to produce the blood vessels which are building up behind the eyes of people with AMD. The siRNA does this by binding to a specific receptor on cell surfaces known as TLR3. However, there are factors that cause this practice to not be implemented today. One of the main issues that scientists and researchers are worried about is that the siRNA might inhibit other types of proteins that are vital for the proper functioning of the human body. After siRNA-027 was abandoned, testing began on another siRNA named Bevasiranib. However, the two year test was deemed unsuccessful after one year and halted. No further siRNA tests have been performed after Bevasiranib, and the future of the siRNA technology is currently unknown. In order for it to be successful siRNA will need to specifically target one goal, without the risk of interfering with important bodily functions.

    • I wrote about the same thing. I felt that blocking blood vessel growth factors would actually be very dangerous. And because the siRNA is administered intravenously this interfering RNA can come in contact with with other vascular blood vessels and inhibit theyre growth.

    • In your post, you talked about Bevasiranib. I also looked into this topic and I from what I read Bevasiranib is Cand5 and this siRNA is doing very well. It has already went through phase I and II of the trials and so far it as been considered safe. From what I read the drug did not escape into the systemic circulation so it is not likely to affect other bodily functions.

  12. RSV or Respiratory syncytial virus is a respiratory illness and anyone can potentially be infected, but RSV most often causes serious illness in infants and very young children, RSV can also cause serious illness in elderly people and people with a weak immune system and RSV infections typically occur during the fall and winter as well as through contact with droplets from the nose and throat of infected people when they cough and sneeze. RSV can also spread through dried respiratory secretions on bedclothes and similar items and typical symptoms resemble the common cold. The biggest problem is that RSV infection can also result in pneumonia, especially in the very young, the very old or those with weakened immune systems but sometimes, mild or unnoticeable illness may occur. Symptoms may persist for a few days to a number of weeks and symptoms generally begin four to six days after exposure. Symptoms generally develop slowly over a period of several days. The contagious period is usually less than 10 days after symptoms begin, but occasionally is longer. ALN-RSV01 a RNAi therapeutic for the treatment of RSV and showed significant anti-viral efficacy. In the Phase II experimental infection study, treatment with ALN-RSV01 led to a decreased RSV infection rate, an increase in the number of subjects who remained free of infection, and was safe and well tolerated, but now a medication called ribavirin is effective against RSV infection if begun in the first few days after symptoms appear. Because RSV infection is often resolved on its own, treatment of mild symptoms is not necessary for most people. Antibiotics are not effective treatments for viral illnesses such as RSV infection.

    • The Age-Related Macular Degeneration siRNA had to be administered intravenously. I wonder how they administer this siRNA. I guess it wouldn’t matter because the respiratory disease is only found in one place, the lungs. Scientist probably would not have to worry about the siRNA interacting with other aveoli cells anywhere in the body since the only place they are found are in the lungs. The AMD blocks vascular blood vessels which are everywhere so this could possibly negatively affect other organs of the body.

    • This post was very informative and easy to understand. I have heard of ribavirin to treat RSV before. I think its is currently the treatment of choice. I was wondering if there is an indication for the uses of ALN-RS01 compared to ribavirin. Is ALN-RS01 just preventative or can it be used to prevent the illness from progressing further by turning off genes.

    • Though brief, I believe your post clearly explained and made it easy to understand the significance of respiratory syncytial virus. I’m surprised as I have never heard of this condition before reading this article, however. Considering the fact that I had a tough bout with asthma and pneumonia, i wonder if I ever suffered from RSV. I wrote a post about ALNRSV01, it’s interesting how it can also be used to treat RSV as well as liver cancer. Possibly, it’s dual efficacy can lead to a faster delivery of the product to the market, with strong scientific research of course.

  13. AMD
    Age related macular degeneration is a medical condition that usually affects older adults. It results in a loss of vision in the center of the visual field because of damage to the retina in the eye, while still leaving decent peripheral vision. It has two forms, wet and dry. It is a major cause of visual impairment in adults over the age of 50. AMD can make it difficult or impossible to do everyday tasks such as read or recognize peoples faces. In the dry form, cellular debris gathers between the retina and the choroid, possibly causing the retina to become detached. In the wet form, which is more severe, blood vessels grow up from behind the retina, also causing the retina to become detached. A company called Acuity Pharmaceuticals produces an siRNA called Cand5. Cand5 shuts down the gene ,vascular endothelial growth factor (VEGF), that promotes the overgrowth of blood vessels that leads to vision loss and AMD. By stopping VEGF, Cand5 is expected to have advantages over other types of therapies for AMD.

    • i thought your disease, AMD was very interesting, but unfortunate condition. I think you did a great job of explaining everything clearly without throwing in ‘big words’ to confuse readers and you explaination of the siRNA product was clear and to the point.

  14. Hepatitis C virus or HCV is an infectious disease of the liver. Though it usally shows no symptoms it can cause scarring of the liver. Over time the scarring can build up and cause liver failure. A person can get Hep C from sex with infected person, blood transfusion, infected tattoo equipment, and dirty needles. In the paper Hepatitis C virus was trying to be cured with Sirna-034 made by Sirna Therapeutics. The drug was suppose to use RNA interference to cure the disease. In the paper written four years ago it was in the preclinical stage of production, I looked it up and it is still in the preclinical stge of production.

    • Hepatitis C unfortunately claims alot of individuals. According to the national foundation for infectious disease, Hepatitis C claims between 8,000 to 10,000 lives annualy. Almost 2% of the United States’ population reports hepatitis C infection, with African Americans and Hispanics representing a significant share of reported cases. Unfortunately, however, hepatitis C virus does its damage even without readily recognizable physical or clinical symptoms. As mentioned, the virus can be transmitted via unprotected sexual intercourse. As a result, the rate of reported cases of Hepatitis C virus is set to increase markedly over the years. It’s unfortunate that there has not been any significant progress in the development of the therapy, considering the danger the virus poses. Hopefully a new therapy can be developed or the existing Sirna-034 can be revised and revitalized.

  15. Respiratory syncytial virus or known as RSV causes infection of the lungs and breathing passages. People of any age can be infected. Very young infants, premature infants, and children with present or previous lung, heart, or immune system problems have a high chance of getting this severe RSV disease. The virus can also cause serious illness in elderly persons and in adults with lung disease or weakened immune systems. In adults it may appear as a common cold with symptoms such as stuffy and runny nose, periodic to chronic sneezes, sore throat, feelings of chills and aching of body parts and sometimes ear infection. Children who develop a lower respiratory tract infection often have low levels of fever for several days and other symptoms which include difficult or rapid breathing and deep coughing. These symptoms that occur in newborns and young infants may exhibit irritability, listlessness, and poor feeding. This infection is transmitted by breathing in the air after an infected person has coughed, hand-to-mouth contact after touching an infected person or a surface that an infected person has touched or coughed on.

    A siRNA product called ALN-RSV01 was developed by Anlynlam to cure RSV and was administered to patients. This siRNA product proves to decrease the rates of contracting the infection and a growing number of people seem to start to be immune to the virus. In order to test if the drug is truly working, an experiment was conducted and was named the Gemini. The experiment consists of 88 adult subjects who were infected with RSV and randomly given either ALN-RSV01 or placebo. Those who have taken the ALN-RSV01 have a significant anti-viral activity with a 38% decrease in RSV infection and also a 95% increase in the number of infection-free subjects who had taken the placebo. This product seems to be hazard-free and tolerable by patients.

    • The trial shows very promising results. Its great that the Gemini showed 38% decrease in RSV infection. The siRNA clearly proves to decrease the rates of infection and an increase in immunity.

    • I like how you related your response to something as common as the cold. It was fascinating to find that this type of virus can be transmitted through the air and yet many people just think of it as a symptom of a common cold. However, it is unclear how we can distinguish the difference between the common cold and the RSV virus.

    • I liked the comparison you made to a common disease. Relating a complicated subject to a much simpler every day thing helps to make this more bearable to read.

  16. The liver is an organ that manages many important processes that contributes to the maintenance of the body’s homeostasis, or the body’s ability to regulate its internal environment. Due to the liver’s importance to the overall physiological condition, any toxicants that can compromise the liver must be approached with carefulness and safety. The liver is a gland, an organ in that synthesizes substances that may cause its effect systemically or locally. The largest of glands, the liver is divided into four lobes, the right lobe, left lobe, quadrate lobe and caudate lobe. Liver cancer is also known as hepatocellular carcinoma, or HCC for short. Liver cells, hepatocytes, make up a great majority of the liver cells mass and structure. As a result, the majority of liver cancers arise from malignancies in the hepatocytes. HCC is often mistaken with secondary liver cancer, a form of cancer affecting the liver, though not originating in the liver. Liver cancer appears to affect to a greater degreee individuals in Southeast Asia and sub-Saharan Africa that in North America and Western Europe.
    Alnylam created a siRNA product for the treatment of liver cancer. The siRNA product, ALN-VSP01 was in it’s preclinical phase at the time of the articles publishing. ALN-VSP is intended to effect KSP and VEGF, two important genes that promote HCC. In 2010, the treatment entered the first phase of testing for treatment of the condition. The result of the dugs battery of testing has been submitted to the CFS (chemotherapy foundation symposium). Delivered by systemic liposomal conjugation, the treatment joins two siRNA’s into a form that targets the two major cancer pathways, VEGF and kinase spindle protein. Studies have shown an marked decline in both size and proliferation of liver tumors.

    • Mr. Morency, I chose the same topic as you, and although the basic knowledge is similiar I did not know that individuals in Southeast Asia and sub-Saharan Africa have a greater percentage of individuals effected than individuals in North America and Western Europe. Isn’t it fascinating how siRNA has the potential of silencing KSP and VEGF and thus blocking cell proliferation?! i hope this concept becomes a reality in the near future!

    • Well constructed response. I wonder why those people have a high chance of getting liver cancer. Maybe because they live in a developing country so their prevention and treatment towards liver cancer might not be up to par.

  17. RNA interference (RNAi) is a naturally occurring mechanism within cells for selectively silencing and regulating specific genes. It represents a hopeful new advance for the inhibition of gene expression in cell culture and in vivo. siRNA is an effective gene-silencing strategy and recent human clinical trials have showed that it can have potential therapeutic effects. Alnylam Pharmaceuticals, Inc. is a leading RNAi therapeutics company. They have been experimenting with human clinical trials to put forward systemically delivered RNAi therapeutic, ALN-VSPO1, for the treatment of liver cancer. Liver cancer is cancer that forms in the tissues of the liver. Worldwide, liver cancer is the most common solid organ tumor, with more than 600,000 people diagnosed each year. Primary liver cancer incidences increase due to underlying liver disease such as hepatitis infection and alcoholism. Liver cancer may be treated with surgery, radiation therapy, or chemotherapy. ALN-VSP01 is an RNAi therapeutic that is designed to target vascular endothelial growth factor (VEGF) and kinesin spindle protein (KSP), which are two genes that are involved in the pathway of tumor pathology, cell proliferation and angiogenesis in a variety of cancers. Therefore, siRNAs can silence these two genes which are critical for tumor proliferation and survival. By blocking the messenger RNA, a disease bearing gene can thus be ‘silenced’ ALN-VSP01 is a RNAi therapeutic that targets these two distinct pathways which can increase the likelihood of achieving clinical benefits for patients. According to the chart, ALN-VSP01 for the treatment of liver cancer is still in its clinical phase. The pre-clinical data showed durable and rapid reduction in vivo of VEGF protein by more than 50% after a single injection of a VEGF-specific siRNA in a rodent model, silencing of KSP mRNA in vivo by a greater than 50% after a single injection of a KSP-specific siRNA in a rodent model, and halting of human cancer cell proliferation in vitro when KSP was silenced by a target-specific siRNA. Alnylam’s RNAi therapeutic, ALN-VSP01 is comprised of two small interfering RNAs or siRNAs, the molecules that mediate RNAi. Each siRNA targets a specific gene in the growth and proliferation of tumors; VEGF which is the key mediator of tumor angiogenesis; and KSP, a protein required for cell division, which when inhibited it leads to cell death in dividing cells. Moreover, ALN-VSP01 is created using Alnylam’s novel liposomal formulation technology. This technology has been used to achieve delivery of siRNAs to cells of the liver and efficient silencing of genes expressed in that organ. There are several reasons why ongoing and planned clinical trials are not moving forward. For example, Rouche decided to end funding of its RNAi research. They found the cell specific delivery to be a big problem in their endeavors. There are also many technical issues involving drug delivery which make the concept of siRNA hard to make into reality. For example, it is difficult to design RNAi drugs which will match the right targets and silence the problem gene and not other genes. Also, siRNA will be degraded before it reaches its target without any chemical modification. Therefore, there must be a system that stabilizes the siRNA molecules. Moreover, it is difficult to gain confidence behind the RNAi mechanism. Although, clinical trials show hopeful results, we do not yet fully understand the action of drugs in humans. Nonetheless, the concept behind siRNA is phenomenal, and if one day scientists could make it a reality, it would be a massive step in our healthcare. However, scientists are still stumbling upon the difficulty of converting the RNAi theory into effective medicines.

    • I found your article interesting. The thought of devising new treatments with new and more advanced techniques is something that a few years ago was not thought of as possible. Using siRNA treatments to cure or even prevent potentially lethal diseases is a goal that many scientists strive for. The daunting task, however, is putting this dream into reality. In the case of liver cancer that affects many patients around the world, it is of a major importance to come to a full and complete understanding of all the different effects of how the treatment will react with the patient. If there are complications with the siRNA targeting specific genes, like you stated, then more research should be done to fix the problems. Once all of the systemtic effects are understood, then attempts to create a treatment for diseases can commence.

  18. Genetics may be the next big upsurge in the future of medicine. Diabetic Macular Edema (DME) is a disease that damages the retina caused by complications of diabetes. It has been seen to occur in patients that have suffered from diabetes for ten years or more, possibly leading to complete blindness. Some causes of diabetic macular edema are poor blood sugar control, elevated lipid levels in the body and severe hypertension. The disease follows the process of the retinal membrane thickening, leading to a breakdown of the retinal barrier. “Thickening of the basement membrane and reduction in the number of pericytes is believed to lead to increased permeability and incompetence of retinal vasculature.” It is this barrier that allows leakage of plasma particles on the surrounding retina, causing retinal edema. There is evidence that this retinal edema is the basis for the production of vascular endothelial growth factor, VGEF. This growth factor allows for propagation of DME ultimately leading to total blindness.
    However, research in the field of ophthalmology, has allowed scientists to create better and more efficient treatments for diseases such as this one. Acuity Pharmaceuticals is an ophthalmic pharmaceutical company that over the course of a few years experimented with a compound besavsiranib sodium, formerly known as Cand5. After explicit testing, Acuity Pharmaceuticals announced that Cand5 showed great results from its phase II status. Besavsiranib is a therapeutical siRNA designed to silence genes that promote expanded blood vessels that lead to loss of vision in patients. This in turn shuts off or silences the growth factor VGEF. Achieving this allows for the besavsiranib to function as both a regulatory drug, by eliminating excess VGEF, and a prevention drug, by stopping the production of VGEF in the eye. The compound was given to 129 patients in 28 states in three doses. What makes this treatment even more helpful is that besavsiranib is administered straight into the eye, showing no particular systematic side effects on the patients.

    • Mike i like the way you described the efffects of DME and the possible alternatives that can be used to treat this deffect. There were a lot of details to back up your claim on the gene therapy utilizing siRNA. Very well thought out and descriptive.

    • I like how descriptive you made your response especially the part when you said, “The disease follows the process of the retinal membrane thickening, leading to a breakdown of the retinal barrier.” Your description was very vivid and imaginable. However I felt that you left us hanging towards the end of you response when you described about the 129 patients. What happened to the people after the administration of the besavsiranib? What was the success rate?

  19. AMD stands for Age Macular Degeneration. This means that as one ages, their vision starts to fail on them slowly with time. AMD usually comes to people after the age of 55. Macula is a region of the eye behind the retina that degenerates leading to this failure to see. There is wet and dry AMD. Wet AMD is when abnormal blood vessels increase in number under the macula which affects the back of the eye; thus, leading to damage. Dry AMD is when sensitive cells in the macula start to degenerate.
    There are treatments, but these treatments are different based on how severe AMD is for that person, which AMD they have, and where, specifically, the blood vessels grow in the eye.
    siRNA (small interference RNA) may be used to stop the growth of these blood vessels, which may prevent AMD. These experiments were done by Allergen and Merck, who have now stopped working together. However, after two trials, the use of siRNA to be an aid for AMD failed to be used because of efficacy issues. Also, with the use of siRNA which stops blood vessels, it may lead to negative effects if siRNA starts to affect vital blood vessels and other important organ vessels besides the ones that must be limited in growth; thus, leading to more consequences than benefits.
    Quark and Pfizer have also done experiments with a siRNA called RTP801i-14. This experiment showed that the use of RTP801i-14 to help AMD lead to no negative effects.
    Negative consequences of using siRNA may be caused due to the fact that siRNA does not work against targets that they were meant to block nor RNA interference.

    • after reading the amd and its causes i feel very unfortunate for the people who carry this gene. i really hope that they would find an actual cure for this disease soon.

  20. The deal in RNA interference (RNAi) therapeutics suggests that there is a continuing study on At027, an siRNA product concerning cancer in the GI tract. Gastrointestinal cancer seem to be fairly common and there are many types that have been found. Gastric cancer and Pancreatic cancer were the two that I found had the better results overall because although they have a potential to aide in cancer death, it is of a smaller amount it effects than other cancers found like cancer of the Bowel (colorectal). The Stomach/Gastric cancer accounts for about 8 per cent of cancer deaths and Pancreatic cancer  accounts for about 4 percent of cancer deaths. The unique properties of Aato27 prevent pulmonary metastasis by working against the protein kinase PKN3 which only served to make things more complicated by promoting the cell growth. The research of the in overall inhibition is in Phase I and for other GI cancers it is in phase II. Bioanantically, this just proves there’s is more to find out about these tumors although we have discovered a potent drug that can effectively sever the process of the unnecessary proliferation.

  21. Liver cancer:
    Liver cancer is also known as primary liver cancer or hepatoma. The liver is made up of different cell types such as, bile ducts, blood vesseles, and fat storing cells. Liver cells make up about 80% of liver tissues. Liver cancer is also the third most common cancer in the world. A deadly cancer, liver cancer is known to kill patients who have it within a year, which is really sad. In 2000, it was estimated that there were about 564,000 new cases of liver cancer worldwide, and a number of patients died as a result of there diseases.
    The role of hepatitis B virus( HBV) infection is causing liver cancer is well established. In patients with both chronic hepatitis and liver cancer, the genetic material of hepatitis B virus is frequently found to be a part of the genetic material of the cancer cells. And that’s how hepatitis B virus cause liver cancer. Drugs, medications, and chemicals play a big role in causing lover cancer. There are no medications that cause liver cancer, but female hormones and protein building are associated with the development of liver cancer. Certain chemicals are associated with other types of cancers found in the liver. There are no specific symptoms of liver cancer, infact the earliest signs are usually difficult to perceive. Abdonimal pain is uncommon with liver cancer and usually signifies a very large tumor or widespread involvement in the liver. Also unexplained weight loss or unexplained fevers are warning signs of liver cancer.

    • Wow, I didnt even know that hepatitis B was a cause of liver cancer, so i found this very interesting. Even though there is no treatment at this time for liver cancer, its good to hear that information about causes and connections are being found and studied.

    • as the reply above i didn’t know that hepatitis B virus causes the liver cancer and that there is no actual cure for this yet. i hope the studies advance faster and results show a promising figure.

  22. AMD the acronym for Age related macular degeneration destroys the central vision of the eye but does not affect the peripheral vision. AMD is unrevirsable and those who have it are unfortunaltly stuck witt this disease. The macular is a light sensitive part of the eye and it can impair our vision eventually leading to blindness. It can possibly lead to the retina being further damaged and become attached. SiRna was a method that was used to regulate gene expression and so it was manipulated as a way to cure AMD. The company Acuity Pharmaceuticals utilized VEGF or (vascular endothelial growth factor) labeled Cand5 which is a siRNA. VEGF regulate leakage of the eye. Patients who undergo this form of gene therapy normally show improvements within three weeks of treatment. VEGF is used to prevent the growth of new blood vessels and if over expressed it could possible lead to disease. There is no cure for AMD and laser surgery seems to be our best bet at this point in time. SiRNA-27 used in gene therapy binds to the target RNA molecule and inhibits expression. Even though patients that have undergo this type of gene expression it has not been able to help all patients. There is still more room for debate on the effectiveness of SiRNA therapy on AMD.

    • Ian I liked your presentation of both sides of the arguement in your writing. You do remind us that although there is room for advancement of treatment with siRNA therapy, there is a possiblity that this treatment might not work for some patients. The fact that scientists do not understand the full effects of these therapies on the human body might be the cause of this occurring. Whatever the case is, siRNA therapy will only be used once our knowledge is complete on all of its capabilites, and when we learn how to elminate all of its flaws.

  23. Diabetic macular edema is the result of retinal microvascular changes which occurs in people with diabetes. Basement membrane thicking & reduction in the number of pericytes is believed to lead to an increased in permeability and incompetence of the retinal vasculature. The compromise of the blood-retinal barrier leads to the leakage of plasma constituents in the surrounding retina which results in retinal edema. The hypoxic state that is achieved can also stimulate the production of vascular endothelial growth factor. There is evidence that VEGF is up-regulated in diabetic macular edema. Some causes include poor control of blood sugar which increases the risk of diabetic retinopathy, renal disease that can be a marker for the development of diabetic retinopathy, & elevated lipid levels which increases the risk of leakage and exudate deposits.
    The standard treatment for diabetic macular edema has been glycemic control which is demonstrated by the Diabetes Control and Complications Trail, optimal blood pressure control that is demonstrated by the United Kingdom Prospective Diabetes Study, and macular focal/grid laser photocoagulation. Laser photocoagulation has been known to reduced the risk of moderate visual loss from diabetic macular edema by 50%. Despite reduced risk, some patients suffer permanent visual loss even after intensive treatment. There are new advances in pharmacotherapy and surgical techniques which have shown promise in the treatment of diabetic macular edema.


    • I think it is interesting how a person would receive the treatment knowing that there is a risk of permanent visual loss. I personally wouldn’t deem it worth losing my vision.

  24. With new problems being discovered often, many researchers and physicians are trying to come up with solutions as quick as possible to help reduce the amount of trouble diseases are causing. One of the major issues is diabetes, which can be categorized as either type I or type II. People who are diabetic may face the possibility of having eye diseases that can develop into diabetic macular edema, or blindness. Development of this disease occurs when blood vessels from the macula starts to leak and the retina, tissues located at the back of the eye, swells up. Before getting diabetic macular edema, many people start off with diabetic retinopathy, changes made to the blood vessels. Diabetic macular edema has two types, each with their own source of treatment. The two are focal and diffuse, one dealing with leakage and the other with dilated retinal capillaries, respectively.
    As of now, the way to treat diabetic macular edema lies in Cand5 and laser treatment. Through laser treatment, thickening of the retina is burned to reduce dilation and to prevent leaks form progressing. Laser treatment also serves to prevent further vision loss. As for Cand5, an RNA molecule that can silence the mRNA encoding for VEGF has entered phase II since 2006, according to Acuity Pharmaceuticals. VEGF is a peptide that promotes vascular permeability, allowing fluids to store up in the retina, causing macular edema. Through Cand5, genes that contribute to the growth of blood vessels are shut down from treatment, helping the diagnosed to avoid blindness. As of today, Acuity Pharmaceuticals continues to use Cand5 an alternative method against diabetic macular edema to help people with diabetes to overcome the chance of having vision loss.

  25. Pandemic Influenza is a global outbreak when a new flu comes to a human population resulting in serious illnesses spreading from one individual to another throughout the world. There is a difference between pandemic flu and seasonal outbreaks because seasonal outbreaks are influenza viruses that already exist and often have vaccines for. But the pandemic flu involves new influenza subtypes that people have not been exposed to recently or often never exposed to before.
    In attempt to prevent a pandemic influenza virus outbreak that could possibly take away the lives of many, Alnylam Pharmaceuticals and researchers from the University of Georgia teamed up (May 2005) to create an RNAi based prevention and treatment. The pharmaceutical company planned on using RNAi (RNA interference) technology to target key flu genes that are required for virus replication. Both the researchers and the pharmaceutical company know the impact that the pandemic flu could potential cause. Professor Ralph Tripp, from the Department of infectious Diseases at University of Georgia, stated “Due to the genetic unpredictability of emerging flu strains, the production of effective vaccines will be difficult, if not impossible…” Knowing that the various viruses have mutated and altered, the researchers want to find a better method in prevention and treatment of a pandemic flu outbreak.
    Ultimately, Alnylam Pharmaceuticals want to create a way for “optimized siRNAs that silence highly sequences required for viral replication across the human and avian flu strains.”

    • This post was very informative and well presented. I felt like you pointed out & explained the major points very well. We must be really careful when treating a seriousness illness such as the flu. Flu viruses are known to transform into new forms and developed a resistant to antibiotics which is why we must continue to do research to combat it. I am glad research is being done on new technology that can’t potential halt new formations of the flu virus.

  26. RNA interference (RNAi) is a natural process that cells use to turn down, or silence, the activity of specific genes. It works by destroying the messengers that contain the information to express the certain gene. It is believed that RNAi functions as a defense mechanism against foreign particles and viruses. The RNAi would inactive the virus’ genes to prevent an infection. This led scientists to research RNAi to combat respiratory infections and cancers. Recently, a new RNAi based drug, Atu027, was tested in a Phase I clinical trial to combat cancers.
    Atu027 has been shown to inhibit lymph node metastasis in prostate cancers in mice. Metastasis is the spread of a diseases from one organ to another, in this case, by lymph nodes. An experiment was administered to test the effectiveness of Atu027 against lung cancer in mice. The drug was compared with small interfering RNA (siRNA) in two experimental lung metastasis models, Lewis lung carcinoma and spontaneous mouse models.
    Results showed that intravenous administration of Atu027 prevented pulmonary metastasis. It was seen that the formation of spontaneous lung metastasis was greatly inhibited with the drug. The overall number of detectable individual tumor cell colonies were less than the sucrose control group. In addition, the weight of the lung was in the proper proportion to the body weight. The scientists feel that the Atu027 can be considered as a future drug to prevent lung metastasis formation. They imply the drug may prove useful in standard cancer therapy.


    Click to access Santel_et%20al_2010_CCR.pdf

  27. Sirna Therapeutics is a biotechnology company that develops therapeutics based on RNA interference technology or siRNA. This company is involved in the research, preclinical, and clinical development with product candidates in different areas, including age-related macular degeneration (AMD), chronic hepatitis, dermatology, asthma, Huntington’s disease, oncology, and diabetes. The company offers a treatment called Sirna-027 which i a completed phase I clinical trial used for the treatment of AMD.
    A multi-targeted siRNA was developed for treatment against Age-related Macular Degeneration (AMD). This product completed a pre-IND meeting on May 14, 2008 with the USFDA approval and IND studies. Scientist have discovered that the disease arises from a VEGF-mediated neovascularization pathway. The disease is therefore considered to be a candidates for treatment by inhibiting this clinically validated pathway at the endothelial cells lining the interior of the growing blood vessels. By using small interfering RNA as an inhibitor, they offer a therapeutic approach combining 25-mer siRNA duplexes targeting VEGF, VEGFR1 and VEGFR2 into one drug candidate, STP601, packaged with a biodegradable polypeptide formulation, for treatment of ocular neovascularization conditions including AMD, PDR and HSK.
    STP601 is an inhibitory drug blocking the production of targeted factors, it will be complementary to the existing antagonist small molecule and monoclonal antibody drugs blocking only the function of the targeted factors, in the same regimen.

  28. RNA interference involves sequence-specific down-regulation or silencing of a target gene by blocking messenger RNA. Short interfering RNA or ‘siRNA’ is a way of harnessing RNA interference to develop new medicines that serve therapeutic purposes. There are several obstacles that must be overcome before the technology can become efficacious, such as creating a sequence that will hit the right target, silencing problem genes and not other normal genes. There must be a way to stabilize the RNA sequence because of the many RNAses present in the body that would degrade it before reaching its target.

    The potential of siRNA to provide antiviral activity has been vastly studied especially in respiratory viruses such as influenza. The flu virus is an RNA virus that passes from animals to humans. Pandemic influenza occurs when a new strain is transmitted from an animal species to humans. Unlike seasonal flu, these strains have are not affected by human immune system and can spread rapidly and infect a large number of people.
    The use of RNAi can be used to specifically target the conserved genes of a virus. As of 2005 Anylam Pharmaceuticals has been researching to discover and develop a ” Direct RNAi therapeuic treatment for the prevention of respiratory infection from newly emerging, highly pathogenic strains of influenza(flu) virus”. They are targeting the genes that are involved with viral replication in hope that it will demonstrate antiviral activity.

  29. AMD terminates the central vision of the eye but keep in contact of the peripheral vision. AMD stands for Age related macular degeneration and cannot be reversed basically meaning those who have AMD is stuck with AMD. What lines most of the structures inside the eye is the macula, a part of the retina. While nerve cells detect light in the retina, macula provides the clear vision. The ability to focus images. To regulate the gene AMD scientist found an answer by using the siRNA. By using VEGF (vascular endothelial growth factor) labeled cand5 to regulated the improvements in the eye within three weeks. It is also used to prevent further growth of new blood vessel which could lead to the disease. However there is still no cure to this disease. There are researches that develop as we speak but the best chances we have is the siRNA and its gene therapy to bind the target RNA.

  30. Respiratory Syncytial Virus is a viral disease that infect the lungs. According to Dr. Krilov, it has been known to manifest itself primarily as bronchiolitis or viral pneumonia. This disease is also the leading cause of respiratory tract infection in infants and young children. The Directors of Health Promotion and Education (DHPE) stated that the disease could be spread through breathing in droplets after an person has coughed, hand-to-mouth contact after touching an infected person, as well as contact with a surface that an infected person had touched/coughed on. Children infected with the disease show symptoms such a cold, stuffy nose, coughing, and can potentially show an ear infection. Adults show similar symptoms, except they also display sinus problems. These symptoms tend to develop with a few days of being infected, and enter into a contagious period within less than ten days.
    RSV is capable of being treated by using ALN-RSV01. Alnylam Pharmaceuticals, Inc., was responsible for developing the siRNA product. ALN-RSV01 has been proven to decrease the infection rate after Alnylam’s phase II experimental study. In addition, the number of subjects who remained free of infection also increase. John Maraganore, Ph.D, Chief Executive Officer of Alnylam stated that their GEMINI project was to establish the anti-viral activity, safety, and tolerability of ALN-RSV01 in an experimental RSV model. Their study used a total of eighty eight adult subjects experimentally infected with RSV, and were randomly given ALN-RSV01 or a placebo. The results show that there was a thirty eight percent reduction in the infection rate, as well as increasing the number of subjects who remained free of infection.

  31. One of the most common cancers is liver cancer. Also known as Hepatocellular carcinoma, Cancer of the liver is very dangerous because you cannot live without your liver. It is one of the most common cancers in the world. Liver cancer has two phases, either primary or secondary cancer. Primary is cancer that just affects the liver or it started in the liver. Secondary cancer of the liver is when cancer is found in the liver but it did not originate in the liver. It can be caused by too much iron in the body, alcohol abuse and diseases affecting the liver.
    Alnylam has been working with short interfering RNAs in order to treat tumors and cancer in the liver. The short interfering RNAs is called ALN-VSP. They are using this ALN-VSP in two key genes that are believed to be involved in promoting liver cancer. One of those is kinesin spindle protein and it is involved in the proliferation of the cancer. The second gene is vascular endothelial growth factor which is involved in new blood vessel growth that feeds the tumors. It is commonly believed that if both are attacked there will be a greater success.
    In April of 2009 there were clinical trials run on 28 patients in which they were given the first six doses. Although the medication is still on trial run the ALN-VSP was well received. In these pre-clinical trials the ALN-VSP was able to silence the kinesin spindle protein and vascular endothelial growth factor genes. They did these tests on animals and they significantly cut down on the number of tumors present in the animals. Those who are taking more and more doses are continuously are getting better and better results.

  32. Liver cancer is a widely known cancer, affecting thousands of humans today. The liver, being one of the largest organs in the human body, consists of four lobes. In the body of a liver cancer patient, it is in these four lobes where the most painful tumors originate. Since tumors are so common in patients suffering from this cancer, Alnylam, a pharmaceutical company, has created a therapeutic called ALN-VSP which keys in on two target genes that are heavily linked with the kinesin spindle protein (a protein that is involved with the rapid reproduction of cancer) and the vascular endothelial growth factor (involved with the proliferation of blood vessels that aid in feeding tumors. Studies showed that the ALN-VSP therapeutic was able to put an end to the rapid reproduction of the cancer cells being formed. There was a distinct reduction in the number of cells in the animals that were being tested. Once we were cleared for experimentation in December of 2008, the first phase was done in April of 2009, on humans. This was simply an evaluation for the liver cancer patients being tested. In June of 2010, it was determined that most of the patients had responded well to the doses given to them. While there were two mild reactions to the therapeutic, it did not progress to the point of danger or death. One patient had died because of hepatic failure fives days after the second dose, however, he was the only patient that had passed away in that point of time. In November 2010, it was evaluated that the patients were still tolerating the therapeutic very well. There were three more reactions to the therapeutic, however those three patients were able to tolerate treatment. Maximum dose was still not reached yet. There has not been any word on the progress of this experiment since November of 2010.


  33. When it comes to siRNA therapies, there is a process which inhibits the synthesis of an encoded protein by targeting a specfic mRNA for degradation. This is known as RNA Interference. When there is degradation of mRNA, it leads to a relivent mechanism for silencing gene expression. One way to achieve this process is by encountering an RNAase III enzyme, which makes this possible by degrading the double-stranded RNA into small fragments, which are most known as small interfering RNA, or siRNA. There have been studies conducted in vitro that require significant features in order for gene silence to proceed without any problems. Some variations of these conditions include: Molecular Weight, Charge, Shape, etc. siRNA must achieve proper delivery to its target sites without causing any effects. Once there it has to be taken up by the cell, avoid any interactions with other orangelles and maintain bioavalibility.

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