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RNA-Targeted Therapeutics.

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.

journal_name

Cell Metab

journal_title

Cell metabolism

authors

Crooke ST,Witztum JL,Bennett CF,Baker BF

doi

10.1016/j.cmet.2018.03.004

subject

Has Abstract

pub_date

2018-04-03 00:00:00

pages

714-739

issue

4

eissn

1550-4131

issn

1932-7420

pii

S1550-4131(18)30182-7

journal_volume

27

pub_type

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