*** 9801382 This Small Business Innovation Research (SBIR) Phase II project will enable custom RNA Synthesis to be affordable, timely, and more powerful through the incorporation of desired modifications. Phase I results demonstrated that novel 5'-silyl-2'-orthoester RNA synthesis chemistry yields authentic RNA oligonucleotides in high yield and of unprecedented quality. However, the utility of this chemistry would be limited if it was restricted to the synthesis of all-ribo oligonucleotides. Market research and ongoing consultations have highlighted the additional need to include modifications. Current commercial RNA synthesis chemistries allow incorporation of modifications, but only chemists and other knowledgeable specialists appear to have significant success with these alternatives. RNA synthesis is not readily accessible to biologists. The achievement of the Phase II objectives will result in 5'-silyl-2'-orthoester chemistry providing the technological leap necessary to make custom RNA synthesis readily available to all biologists. This will require both incorporating desired modifications and decreasing synthesis costs and turnaround times. The result will be the ready accessibility of custom RNA synthesis to the entire scientific community for a wide range of applications. Project success will satisfy the needs of the research community for affordable, reliable, custom synthesis of RNA toward numerous applications. ***
