*** 9760309 Scaringe This Small Business Innovation Research Phase I project will evaluate the effectiveness of non-porous polystyrene beads derivatized with branched linkers to yield a high loaded support to be used in conjunction with an efficient RNA synthesis chemistry. This support will enable (1) large scale RNA syntheses and (2) syntheses of RNA up to 120 bases.The company is successfully developing an RNA chemistry in which each nucleotide couples in less than 90 seconds with yields in excess of 99%. 36-Nucleotide RNA oligonucleotides are functional sites on the external and internal surfaces of porous polystyrene beads. Unfortunately, the pores constrain the amount and length of RNA that can be synthesized. Large syntheses and long sequences are unfeasible with this chemistry on porous support. Development of a suitable non-porous bead is proposed.. Oligonucleotides would grow out into solution without limitations of length. Branched linkers would multiply functional surface sites for large syntheses. These supports will be evaluated with the existing RNA chemistry to synthesize larger scales and longer sequences. Project success will satisfy research and pharmaceutical market needs for large scale RNA syntheses and routine synthesis of RNA less than or equivalent to 120 bases long. These more powerful RNA synthesis capabilities will help the biotechnology and health care industries in investigating RNA-based therapeutics. ***