New Reagents for Synthesizing Nuclease-resistant siRNA

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 1R43GM084552-01
Agency Tracking Number: GM084552
Amount: $199,202.00
Phase: Phase I
Program: SBIR
Awards Year: 2008
Solicitation Year: 2008
Solicitation Topic Code: N/A
Solicitation Number: PHS2007-2
Small Business Information
AM BIOTECHNOLOGIES, LLC
AM BIOTECHNOLOGIES, LLC, 12521 Gulf Freeway, Houston, TX, 77034
DUNS: 788679244
HUBZone Owned: Y
Woman Owned: Y
Socially and Economically Disadvantaged: Y
Principal Investigator
 () -
Business Contact
Phone: (281) 794-2333
Email: mark.shumbera@thioaptamer.com
Research Institution
N/A
Abstract
DESCRIPTION (provided by applicant): The siRNA molecule needs better protection from nuclease degradation before it can be effectively used as a therapeutic. AM Biotechnologies (AM) will address this critical issue by developing ribonucleoside thiophospho ramidite (ABz, CBz, GIbu and U) reagents that will enable synthesis of phosphorodithioate siRNA (PS2-siRNA). This synthesized PS2-siRNA will significantly increase siRNA nuclease resistance; lower Tm, which could help the activated RISC unwind siRNA; and e nhance the pharmacokinetic properties of siRNA. The PS2-siRNA will also be achiral at phosphorus, which will eliminate the variable biochemical, biophysical, and biological properties of diastereomeric phosphoromonothioate substituted siRNAs (PS-siRNAs). I n this Phase I SBIR project, AM will: 1) develop the chemistry and optimize the conditions to produce four ribonucleoside thiophosphoramidites (ABz, CBz, GIbu and U); 2) demonstrate high coupling yield (gt97%) in the synthesis of PS2-siRNAs; and 3) evaluat e PS2-siRNA gene silencing effect in vitro. In Phase II, AM will perform the research required to (a) scale reagent production up to commercial quantities and purity; (b) optimize a robust protocol for synthesis of PS2-siRNA; (c) systematically evaluate th e positional effect of PS2 modification on siRNA activity in mammalian cells; (d) examine the bio-distribution of PS2-siRNA; and (e) fully characterize the pharmacokinetic properties of PS2-siRNA. AM in Phase II may also offer for sale limited quantities o f research-grade reagents for market beta testing. Upon successful completion of Phase II, AM will work with its industry partners to commercialize the ribonucleoside thiophosphoramidites (R-thioamidites) and enable the entire life science community to ben efit from the use of these unique reagents.

* information listed above is at the time of submission.

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