Predicting oligonucleotide therapeutic efficacy at the population level

Pantazis I. Theotokis, Louise Usher, Christopher K. Kortschak, Ed Schwalbe, Sterghios Moschos

Research output: Contribution to journalMeeting Abstractpeer-review


BACKGROUND: DNA-directed RNA interfering (RNAi) mediators that follow the classic Watson-Crick base pairing to bind to their molecular targets and exert their silencing capacities have been identified to be relatively insensitive to single nucleotide polymorphisms (SNPs). The experimental evaluation of a few putative genomic SNPs in a quasi-species population is the only approach scientists have been employing so far for the experimental validation of the efficacy of oligonucleotide drugs on a given population. These studies are inherently constrained by the number of SNPs that can be experimentally supported in the context of an identified molecular target. MATERIALS AND METHODS: To address this sampling limitation, we have developed a method to report the relative sensitivity of all known and unknown polymorphisms to a prospective therapeutic drug. The power of ultra-deep next generation sequencing (NGS) allows us to test drug effect in vitro on all possible SNPs of a molecular target, in a patient-free manner. We are presenting the technical details to our approach that is empowering unbiased pharmacodynamic studies at the population level for sequence-specific oligonucleotide drugs and genome editing tools.

Original languageEnglish
Pages (from-to)182
Number of pages1
JournalHellenic Journal of Nuclear Medicine
Issue numberSupplement 2
Publication statusPublished - 1 Nov 2019


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