Editorial focus: understanding off-target effects as the key to successful RNAi therapy

Rafal Bartoszewski; Aleksander F Sikorski

doi:10.1186/s11658-019-0196-3

Editorial focus: understanding off-target effects as the key to successful RNAi therapy

Cell Mol Biol Lett. 2019 Dec 9:24:69. doi: 10.1186/s11658-019-0196-3. eCollection 2019.

Authors

Rafal Bartoszewski¹, Aleksander F Sikorski²

Affiliations

¹ 1Department of Biology and Pharmaceutical Botany, Medical University of Gdansk, Gdansk, Poland.
² 2Department of Cytobiochemistry, Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland.

Abstract

With the first RNA interference (RNAi) drug (ONPATTRO (patisiran)) on the market, we witness the RNAi therapy field reaching a critical turning point, when further improvements in drug candidate design and delivery pipelines should enable fast delivery of novel life changing treatments to patients. Nevertheless, ignoring parallel development of RNAi dedicated in vitro pharmacological profiling aiming to identify undesirable off-target activity may slow down or halt progress in the RNAi field. Since academic research is currently fueling the RNAi development pipeline with new therapeutic options, the objective of this article is to briefly summarize the basics of RNAi therapy, as well as to discuss how to translate basic research into better understanding of related drug candidate safety profiles early in the process.

Keywords: Off-target effects; RNAi drug candidates; RNAi therapy; microRNAs; ncRNAs; siRNAs.

Publication types

Review

MeSH terms

Amyloid Neuropathies / genetics
Amyloid Neuropathies / metabolism
Amyloid Neuropathies / pathology
Amyloid Neuropathies / therapy*
Animals
Gene Transfer Techniques
Humans
MicroRNAs / antagonists & inhibitors
MicroRNAs / genetics
MicroRNAs / metabolism
Molecular Targeted Therapy / methods
RNA Interference*
RNA Stability
RNA, Messenger / antagonists & inhibitors
RNA, Messenger / genetics*
RNA, Messenger / metabolism
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
RNA, Small Interfering / therapeutic use*
RNA, Untranslated / antagonists & inhibitors
RNA, Untranslated / genetics
RNA, Untranslated / metabolism
RNA-Induced Silencing Complex / genetics
RNA-Induced Silencing Complex / metabolism
RNAi Therapeutics / methods*

Substances

MicroRNAs
RNA, Messenger
RNA, Small Interfering
RNA, Untranslated
RNA-Induced Silencing Complex
patisiran