Poster abstracts
Poster number 128 submitted by Michael Brennan
Synthesis of higher order oligonucleotides for therapeutic investigations
Michael Brennan (Oligrow, Nitto Denko Avecia, Cincinnati, OH), Tim Efthymiou (Oligrow, Nitto Denko Avecia, Cincinnati, OH), Carol Kirby (Oligrow, Nitto Denko Avecia, Cincinnati, OH), Amanda Magrino (Oligrow, Nitto Denko Avecia, Cincinnati, OH), Daniel Tener (Oligrow, Nitto Denko Avecia, Cincinnati, OH), Huihe Zhu (Oligrow, Nitto Denko Avecia, Cincinnati, OH)
Abstract:
Aside from promising developments of siRNA and antisense technologies, higher order oligonucleotide structures are becoming a new field of interest for therapeutic purpose. Among them, tRNAs have been found to potentially treat nonsense mutation-associated diseases; tRNAs can override premature stop mutations and reproduce functional proteins. Another area is circular DNA/RNAs. With finding more circular RNAs in humans, cyclic DNA/RNA oligonucleotides are explored as both biological tools and potential therapeutics due to their good serum and thermal stabilities. To keep up with these new potentials in the field, we explored different routes, such as chemical ligation, enzymatic ligation, and/or linear synthesis, to manufacture such compounds from a process perspective. This poster has two parts. We will show the successful process development for a complete circular loop oligonucleotide (100 mg) using chemical ligation. The second part compares production of a modified tRNA using the standard linear construction through solid phase approach to an enzymatic approach where two smaller sequences are joined to make the longer 76-mer. From the analysis of the initial process development activities, a process for a 5 gram manufacture was chosen based on yield, impurity profile, and cost of goods.
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