Poster abstracts
Poster number 117 submitted by Austin Rockaitis
Using an Electrochemical Deblocking Step in ASO Synthesis to Produce Quicker and Higher Yields of Oligonucleotides
Austin Rockaitis (Chemistry), Daniel Kissel (Chemistry)
Abstract:
Machado Joseph Disease is an autosomal dominant genetic disease caused by excessive glutamine repeat in the Ataxin protein. To treat the repeating protein, oligonucleotides are synthesized that act as primers to create new strands of DNA or RNA to correct the genetic sequence causing the disease. The conventional synthesis method requires a five-step approach, using phosphoramidites anchored to solid supports. Deblocking is the first step of this cycle, where the phosphoramidite blocking agent is chemically removed. Traditionally, dichloroacetic acid in methanolic acid is used to remove the blocking group, N, N-Dimethyltryptamine, and replace it with a reactive alcohol group. The efficiency of the deblocking step can vary depending on a variety of factors including the amount of experience the experimenter has, the purity of the reagents, and the amount of time needed for the reaction. Using an electrochemical deblocking step, however, limits the number of factors by delivering the acid to a specific region on the Phosphoramidite thereby directing nucleotide addition at a chosen site. Creating a more direct addition allows for more precise synthesis resulting in higher yields and more complex oligonucleotide chains. This work reports the synthesis and characterization of a novel ASO synthesized using an electrochemical deblocking step.
Keywords: ASO, Deblocking, oligonucleotides