Developing Small Molecules to Potentiate RNA Interference

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$115,422.00
Award Year:
2009
Program:
STTR
Phase:
Phase I
Contract:
1R41EY018967-01A2
Award Id:
93763
Agency Tracking Number:
EY018967
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
EFFIGENE PHARMACEUTICALS, INC., c/o Emtech Bio, ATLANTA, GA, 30306
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
808050327
Principal Investigator:
PENG JIN
() -
Business Contact:
WEI XHANG
() -
wei_zhang@effigene.com
Research Institution:
EMORY UNIVERSITY

EMORY UNIVERSITY
1599 CLIFTON ROAD, 4TH FLOOR
ATLANTA, GA, 30322 9472

Nonprofit college or university
Abstract
DESCRIPTION (provided by applicant): SiRNAs are synthetic double-stranded oligonucleotides of ~21 base pairs. When applied to cells, siRNAs can effectively and specifically silence their target genes, called RNA interference (RNAi). RNAi has become attract ive tool for functional genomics and a potential class of molecules for human therapeutics. However, almost every siRNA drug company encounters several hurdles, mainly the high dose of siRNA needed for human trials with which come potential side effects, a nd off-target effects of siRNA molecules. The latter is believed to be resolvable by clever design of siRNA molecules. There are no solutions for the former at the moment. To address these difficulties associated with siRNA therapy, we have identified an R NAi-enhancer that can raise siRNA efficacy, lower the required siRNA dose, and prolong its silencing effect. If successfully developed, these enhancers could be used as an adjuvant therapy with siRNA drugs. Age-related macular degeneration (AMD) is a condi tion in which cells of the macula lutea degenerate, resulting in blurred vision and ultimately blindness. AMD is the leading cause of blindness in people over age 50, with 200,000 new cases reported annually in US. To date, two siRNAs have been developed f or the treatment of AMD. As a result, the full efficacy of current siRNA drug candidates for AMD may not yet be achieved. In this Phase I STTR proposal, we will examine whether RNAi-E can enhance the efficacy of siRNAs to treat AMD in a mouse model, which will provide the proof-of-principle demonstration that RNAi-E could be used as an adjuvant therapy along with siRNA drugs. We will determine the optimal concentration of an RNAi-enhancing compound (RNAi-E) to potentiate chemically modified siRNA molecules in an in vitro system and determine the feasibility of RNAi-E for enhancing siRNA efficacy in vivo. Phase II of this project will entail IND enabling formulation, pharmacokinetics and toxicology studies that advance the leading compound(s) into human clini cal trials. If these studies are successful, this would be a major stride toward the improvement of siRNAs for use as therapeutic reagents. PUBLIC HEALTH RELEVANCE: This Phase I STTR application is focused on the development of an adjuvant therapy with the siRNA drugs for human diseases based on the identification of an RNAi-enhancer that can raise siRNA efficacy, lower the required siRNA dose, and prolong its silencing effect. The proposed studies would be a major stride toward the improvement of siRNAs fo r use as therapeutic reagents to treat human diseases.

* information listed above is at the time of submission.

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