IMPROVED PROCEDURE FOR THE SOLID PHASE SYNTHESIS OF OLIGONUCLEOTIDES

摘要

An improved method of solid phase oligonucleotide synthesis is presented. The method results in lesser contamination of the final product with N-1, N-2, and other failure sequences. The method comprises employing a second capping step after initial loading and capping of the solid support and before addition of the second nucleoside. Further diminution in the N-1 oligonucleotide content can be realized when this second capping stepped is used in combination with loading the support to higher densities than have previously been deemed acceptable and by cleaving the full length oligonucleotide from the solid support using mildly basic conditions.