RNA Specific Oligonucleotide

Period of Performance: 08/01/1994 - 07/31/1995

Unknown

Phase 2 SBIR

Recipient Firm

Dyad Pharmaceutical Corporation
Columbia, MD 21046
Principal Investigator

Abstract

The use of antisense oligonucleotides for regulation of gene expression has received widespread attention as a new class of potential chemotherapeutic agents. Many oligonucleotide analog structures have been studied for this purpose. There is presently no universally applicable oligonucleotide structure to serve as an antisense effector. The SBIR Phase I demonstrated the feasibility of a unique class of oligonucleotide analogs comprised of a novel internucleosidic linkage. The oligonucleotide analog incorporates a sugar-phosphate backbone modification that retains the Watson-Crick base-pairing properties, aqueous solubility and achirality of natural oligodeoxynucleotides, however confers greater stability to exo- and endonucleolytic degradation. An interesting feature of the oligonucleotide analog is the nucleic acid specificity. The results of thermal denaturation studies reveal binding to complementary RNA comparable to the natural oligodeoxynucleotide congener, however no binding to complementary DNA is observed. This is in contrast to most antisense oligodeoxynucleotide analogs including those under clinical evaluation, e.g., methyl phosphorate, phosphorothioate, which hybridize to both RNA and DNA. The primary focus of the Phase II is to determine if the RNA specificity observed in this new class of oligonucleotide analogs represents an important design feature to improve the efficacy of antisense therapeutics.