Chemical Synthesis of RNA via Novel Strategy

Period of Performance: 06/01/1997 - 11/30/1997


Phase 1 SBIR

Recipient Firm

Dharmacon, Inc.
Lafayette, CO 80026
Principal Investigator


The growing interest in RNA structural components, ribozymes and other RNA functions has generated a need for reliable methods of synthesizing small RNA oligonucleotides (less than 50 nucleotides). Although RNA synthesis can be accomplished for some applications by knowledgeable specialists via either biochemical methods, e.g. transcription, or chemically, e.g. 5'-dimethoxytrityl-2'-silyl chemistry, there is a definite need for improved RNA synthesis methods. RNA synthesis would be considerably more powerful if readily accessible to biologists, who play central roles in driving advances in health-related research. Final processing of synthesized RNA must be done under mild, sterile conditions with minimal handling. Our final processing is accomplished under mild aqueous conditions, pH 3, 55 angstroms C for 10 minutes. The purpose of this study is twofold: (1) establish that this chemistry can be made commercially available, i.e. research and develop the novel protecting group so that they are amenable to large scale economical synthesis, (2) establish the general utility of this chemistry by synthesizing a variety of RNA oligonucleotides to be evaluated by several collaborators. Accomplishment of these goals would sastify the market need in the research community for ready access to RNA oligonucleotides.