Study: RNAi silencing strategy blocks production of mutant huntingtin protein

In continuation of my update on RNAi

A targeted gene silencing strategy blocks production of the dysfunctional huntingtin (Htt) protein, the cause of Huntington's disease, a fatal, inherited neurodegenerative disorder. The effectiveness of this RNA interference (RNAi) approach in reducing levels of mutant Htt protein and disease symptoms in a mouse model of the disease is described in Human Gene Therapy, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available free on the Human Gene Therapy website.

Lisa Stanek and coauthors from Genzyme (Framingham, MA) used an adeno-associated viral (AAV) vector to deliver a targeted nucleic acid sequence called a small interfering RNA (siRNA) into the cells of affected mice. The siRNA selectively binds to the mutated gene, blocking disease-causing Htt production. The authors present data demonstrating the ability to deliver the therapeutic RNAi into the cells, reduce mutant Htt levels, and impact behavioral deficits in the mice without causing any noticeable neurotoxicity, in their article "Silencing Mutant Huntingtin by Adeno-Associated Virus-Mediated RNA Interference Ameliorates Disease Manifestations in the YAC128 Mouse Model of Huntington's Disease."

"The Genzyme group uses state-of-the-art delivery technology and a gene silencing approach to generate very promising preclinical data for Huntington's disease," says James M. Wilson, MD, PhD, Editor-in-Chief of Human Gene Therapy, and Director of the Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia.

Study: RNAi silencing strategy blocks production of mutant huntingtin protein

Scientists discover new mechanisms by which RNA drugs can control gene activity

 In continuation of my update on RNAi

Short strands of nucleic acids, called small RNAs, can be used for targeted gene silencing, making them attractive drug candidates. These small RNAs block gene expression through multiple RNA interference (RNAi) pathways, including two newly discovered pathways in which small RNAs bind to Argonaute proteins or other forms of RNA present in the cell nucleus, such as long non-coding RNAs and pre-mRNA. 

Keith T. Gagnon, PhD, and David R. Corey, PhD, University of Texas Southwestern Medical Center, in Dallas, review common features shared by RNAi pathways for controlling gene expression and focus in detail on the potential for Argonaute-RNA complexes in gene regulation and other exciting new options for targeting emerging forms of non-coding RNAs and pre-mRNAs in the article "Argonaute and the Nuclear RNAs: New Pathways for RNA Mediated Control of Gene Expression." 

"The field of RNA mediated control of gene expression is rapidly evolving and the article by Gagnon and Corey provides a highly informative and up to date review of this exciting and often surprising area of biomedical research. We are delighted to publish this important review for the field," says Co-Editor-in-Chief Bruce A. Sullenger, PhD, Duke Translational Research Institute, Duke University Medical Center, Durham, NC.

Ref : http://www.liebertpub.com/global/pressrelease/new-rna-based-therapeutic-strategies-for-controlling-gene-expression/987/

New data on novel gene-silencing oligonucleotide technology...

Idera announced new data on its novel gene-silencing oligonucleotide (GSO) technology at the Cell Symposium on Regulatory RNAs in Chicago, IL. In preclinical studies, systemic delivery of GSOs targeted to ApoB or PCSK9 mRNA caused a reduction in the level of the targeted mRNA and associated protein and resulted in a decrease in serum total cholesterol and LDL-cholesterol concentration. ApoB and PCSK9 are two validated targets associated with cardiovascular diseases.

In this study, Idera created 19mer GSOs for apolipoprotein B (ApoB) and proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA and evaluated their in vivo activity in mice following subcutaneous administration. The data demonstrate that treatment with each GSO led to a significant reduction in the concentration of the target associated mRNAs and protein. The effects were specific, with no significant effects being observed on ABCA1, ABCG1 or LXR mRNA levels. In addition, treatment with GSOs for either ApoB or PCSK9 resulted in a decrease in total serum cholesterol and LDL-cholesterol. 

More...

Scientists determine how RNAi, a biological response to RNA, can regulate gene expression

Scientists determine how RNAi, a biological response to RNA, can regulate gene expression

New RNA interference technique can silence up to five genes

New RNA interference technique can silence up to five genes

Cequent Pharmaceuticals proposes the first test of an orally administered RNA interference drug in humans

Cequent Pharmaceuticals proposes the first test of an orally administered RNA interference drug in humans

Report on the future of RNAi-based therapeutics & diagnostics

The market for RNAi-based therapeutics is forecast to grow from 2013 onwards, as the first products enter the marketplace, to generate sales in excess of US$2.9 billion by 2020. The first siRNA based therapeutics will capitalize on the demand to treat viral infections and ocular conditions and in the longer term companies will be able to target niche areas of high unmet clinical need such as cancer, cardiovascular disease, metabolic disorders, inflammatory and neurological conditions.

More.....Report on the future of RNAi-based therapeutics & diagnostics

Using RNAi-based Technique, Scientists Find New Tumor Suppressor Genes In Lymphoma...

In one of my earlier blog about RNAi, I did mention about the award of USPTO notices to RXi Pharmaceuticals Corporation. But these results are really interesting, the CSHL team’s discovery stems from their use of a powerful technology called RNA interference (RNAi), which suppresses gene activity. The scientists employed RNAi to screen hundreds of candidate tumor-suppressors in living mice, using small hairpin-shaped RNA (shRNA) molecules that attach to specific genes with exquisite specificity and switch them off. In the newly reported experiments, this process revealed more than 10 genes whose deactivation accelerates the development of deadly lymphomas tumors of the immune system in the mice.

The CSHL team’s high-throughput screening strategy to functionally identify cancer genes has thus not only provided insights into cancer development but has also pointed the way toward therapeutic refinements. The team is planning a broader RNAi-based screen that will expand into other tumor models. For details...

RXi receives USPTO notices of allowance for certain siRNA sequence-specific patent applications..

In my earlier blog (January 25, 2009), titled "Diverse use of Nucleic acids....." I did mention about the RNA interference (RNAi) technology. Yes the dream has come true now "RXi Pharmaceuticals Corporation" has received Notices of Allowance from USPTO for small interfering RNA (siRNA) sequences targeting superoxide dismutase (SOD1), Amyloid beta (A4) precursor protein (APP), interleukin-1 receptor-associated kinase 4 (IRAK4), hepatocyte growth factor receptor (MET protooncogene) and cyclin-dependent kinase (cdk) inhibitor p27 (also known as MET protooncogene). Hope these class of compounds will get a boost and some new drugs from these class of compounds in the near future.....

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RXi receives USPTO notices of allowance for certain siRNA sequence-specific patent applications

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