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Review
. 2018 Apr 3;27(4):714-739.
doi: 10.1016/j.cmet.2018.03.004.

RNA-Targeted Therapeutics

Stanley T Crooke  1 , Joseph L Witztum  2 , C Frank Bennett  3 , Brenda F Baker  3
Affiliations
Free article
Review

RNA-Targeted Therapeutics

Stanley T Crooke et al. Cell Metab. .
Free article

Erratum in

  • RNA-Targeted Therapeutics.
    Crooke ST, Witztum JL, Bennett CF, Baker BF. Crooke ST, et al. Cell Metab. 2019 Feb 5;29(2):501. doi: 10.1016/j.cmet.2019.01.001. Cell Metab. 2019. PMID: 30726759 No abstract available.

Abstract

RNA-targeted therapies represent a platform for drug discovery involving chemically modified oligonucleotides, a wide range of cellular RNAs, and a novel target-binding motif, Watson-Crick base pairing. Numerous hurdles considered by many to be impassable have been overcome. Today, four RNA-targeted therapies are approved for commercial use for indications as diverse as Spinal Muscular Atrophy (SMA) and reduction of low-density lipoprotein cholesterol (LDL-C) and by routes of administration including subcutaneous, intravitreal, and intrathecal delivery. The technology is efficient and supports approaching "undruggable" targets. Three additional agents are progressing through registration, and more are in clinical development, representing several chemical and structural classes. Moreover, progress in understanding the molecular mechanisms by which these drugs work has led to steadily better clinical performance and a wide range of mechanisms that may be exploited for therapeutic purposes. Here we summarize the progress, future challenges, and opportunities for this drug discovery platform.

Keywords: GalNAc; RNAi; anti-miRs; antisense; oligonucleotide; siRNA.

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