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Funding News - Research to Improve the Chemistry and Targeted Delivery of RNAi Molecules Sought

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The National Institute of Neurological Disorders and Stroke (NINDS) invites small business innovation research (SBIR) and small business technology transfer (STTR) grant applications to develop new approaches and chemical modifications to increase the long-term stability, delivery, and targeting of siRNAs (short-interfering RNA) in cells and tissues for laboratory and therapeutic applications. This announcement is made together with 12 other components of the National Institutes of Health (NIH).*

RNA interference (RNAi) has emerged as a powerful strategy for silencing genes and has become a widely used tool due to its great simplicity and high efficiency. The possible therapeutic applications of RNAi are broad and far reaching, ranging from acquired diseases, such as viral infections, to genetic disorders, particularly where there is a dominant gain-in-function mutation. The discovery of RNAi has revolutionized genetic research, and is on the verge of spawning an entirely new class of drugs to treat human genetic diseases, provided that significant barriers in delivery and targeting can be overcome.

Research areas of interest include, but are not limited to, studies to develop: nucleic acid modifications leading to resistance to nuclease digestion but still allowing efficient processing by Dicer; chemical modifications that enhance base-pairing interactions between the siRNA and targeted mRNA; chemical modifications that will allow or regulate distribution to target tissues, such as to and across the blood-brain barrier; improved instrumentation that will synthesize long oligonucleotides reliably and with high fidelity; and systems for conditional expression of siRNAs. Also of interest are studies to: develop and identify chemical modifications to improve thermal stability of dsRNA, such as LNA (locked nucleic acids) or HNA (hexitol nucleic acids); identify chemical modifications leading to preferential strand uptake by RISC that will enhance specificity and reduce off-target effect; and identify chemical modifications, such as phosphorothioate linkages that will enhance the pharmacokinetic properties of siRNA.

For more information, potential applicants should contact Dr. Danilo Tagle, Program Director, Neurogenetics Cluster, NINDS, Neuroscience Center, 6001 Executive Boulevard, Room 2133, Bethesda, MD 20892; telephone: 301-496-5745; fax: 301-402-1501; e-mail: dt39y@nih.gov.

*For a full list of supporting NIH components and a more detailed description of this program announcement, please visit the NIH web site at: http://grants.nih.gov/grants/guide/pa-files/PA-06-003.html.