Ribonucleases as Drug Targets

Trends in Pharmacological Sciences
Emanuele Canestrari, Zain Paroo

Abstract

Across disease indications, there is immediate need for new drug targets. Target scarcity is reflected in a growing number of same-target drugs of marginal clinical value. Advances in RNA mechanisms of disease are revealing a windfall of targets for nucleic acids therapeutics. However, nucleic acids remain limited as pharmaceutical agents. Because enzymes are predominant drug targets, ribonucleases represent an established target class to capitalize on RNA mechanisms of disease. Analysis of the human proteome identified 122 ribonucleases. This small ribonucleome mediates the biosynthetic and catabolic processing of a large transcriptome. Thus, ribonucleases represent critical signaling targets. Similar to kinases, proteases, and epigenetic enzymes, ribonucleases are rational targets for development of therapies with novel mechanisms, expanding treatment options for improved patient outcomes.

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