The growing interest in RNA oligonucleotides both as tools in biological research and as potential therapeutic agents has generated a need for a reliable and cost- effective mean to synthesize long RNA oligonucleotides (120 bases) and large scales (1000 pmoles). These RNA synthesis capabilities will be of immense value to health-related research and to therapeutics development. Dharmacon Research, Inc. is successfully developing an RNA chemistry in which each nucleotide couples in <90 seconds with >99% yields. 36- Nucleotide long RNA's are routinely synthesized in >70% overall yield. The RNA chains are synthesized stepwise from 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 (>40 bases) are unfeasible using Dharmacon's chemistry on porous polystyrene supports. They propose to develop a suitable non-porous bead. Oligonucleotides would grow into solution without limitations of length. Branched linkers would multiply functional surface sites for large syntheses. These supports will be evaluated using Dharmacon's RNA chemistry and will enable (1)large scale RNA syntheses and (2) syntheses of RNA up to 120 bases.
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