Predicting oligonucleotide therapeutic efficacy at the population level.

Autor:	Theotokis PI; National Heart and Lung Institute, Imperial College, London, Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle, Tyne and Wear, NE1 8ST, UK. sterghios.moschos@northumbria.ac.uk., Usher L, Kortschak CK, Schwalbe E, Moschos SA
Jazyk:	angličtina
Zdroj:	Hellenic journal of nuclear medicine [Hell J Nucl Med] 2019 Sep-Dec; Vol. 22 Suppl 2, pp. 182.
Abstrakt:	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.
Databáze:	MEDLINE
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