Journal Article

MOPSS: Toward high‐fidelity oligonucleotides for clinical applications

Choi, Yeongjae, Choi, Hansol, Ryu, Taehoon, Kwon, Sunghoon

2022

Overview

The United States Food and Drug Administration (FDA) has approved several oligo-based therapeutics, and more than 155 active clinical trials are currently ongoing, advancing the clinical use of oligos as a paradigm-shifting methodology.1,2 When utilizing oligos in clinical applications, fidelity is one of the most critical criteria affecting their performance.3 Oligos are synthesized by coupling oligo monomers individually, following the desired sequence. Errors in oligo sequences, including deletions, insertions, and substitutions, inevitably occur during synthesis, since the monomer coupling is not 100% efficient.4 For therapeutical uses, oligos are either hybridized to the target gene, genome, or RNA to regulate or edit gene expression (e.g., ASO, siRNA, sgRNA) or are translated in vivo to be utilized as a drug or immune stimulatory molecule (e.g., mRNA vaccine). [...]MOPSS does not require any additional (dummy) sequences for purification and can be applied to oligos of various purposes, because the nucleotide-recognizing region is located at a pre-existing site (e.g., primer sequence). [...]we applied MOPSS to digital data encoded oligos, synthetic antibody encoding oligos, and human genome capture oligos from a previously reported article.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
• Subject: Automation / Clinical medicine / Gene expression / Genomes / Hybridization / mRNA vaccines / Oligonucleotides - therapeutic use