SBIR Phase I: Novel Chemical Synthesis of Ribo Nucleic Acid (RNA) Oligonucleotides

本项目将评估使用一种新的化学合成方案合成的RNA寡核苷酸的质量和效用。随着人们对RNA结构成分、核糖酶和其他RNA功能的兴趣日益增长，对合成小RNA寡核苷酸（50个核苷酸）的可靠方法产生了需求。虽然RNA合成可以通过生化方法（如转录）或化学方法（如5'-二甲氧基三烷基-2'-硅基化学）完成，但确实需要改进RNA合成方法。合成RNA的最终处理必须在温和、无菌的条件下进行，处理最少。我们的最终处理是在温和的水条件下完成的，pH值为3,55 ÝC 10分钟。本研究的目的有两个：(1)通过合成各种RNA寡核苷酸来建立这种化学的一般效用，并由几位合作者进行评估；(2)通过使用广泛的化学和生化分析来确认RNA的质量。如果这种具有成本效益的途径能够开发出来，寡核苷酸的市场应该会显著增长到数百万美元的水平。

This project will evaluate the quality and utility of RNA oligonucleotides synthesized using a novel chemical synthesis scheme. The growing interest in RNA structural components, ribazymes and other RNA functions has generated a need for reliable methods of synthesizing small RNA oligonucleotides (50 nucleotides). Although RNA synthesis can be accomplished for some applications via either biochemical methods, em. transcription, or chemically, e.g. 5'-dimethoxytrityl-2'-silyl chemistry, there is a definite need for improved RNA synthesis methods. 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 ÝC for 10 minutes. The purpose of this study is twofold: (1) establish the general utility of this chemistry by synthesizing a variety of RNA oligonucleotides to be evaluated by several collaborators, (2) confirm the RNA quality by using a broad spectrum of chemical and biochemical assays. The market for oligonucleotides should grow significantly to a multi-million dollar level if this cost effective route to these materials can be developed.