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Review
. 2022 Jul 6;8(1):e10374.
doi: 10.1002/btm2.10374. eCollection 2023 Jan.

RNA therapeutics in the clinic

Alexander Curreri  1   2 , Disha Sankholkar  3 , Samir Mitragotri  1   2 , Zongmin Zhao  4   5
Affiliations
Review

RNA therapeutics in the clinic

Alexander Curreri et al. Bioeng Transl Med. .

Abstract

Ribonucleic acid (RNA) therapeutics are being actively researched as a therapeutic modality in preclinical and clinical studies. They have become one of the most ubiquitously known and discussed therapeutics in recent years in part due to the ongoing coronavirus pandemic. Since the first approval in 1998, research on RNA therapeutics has progressed to discovering new therapeutic targets and delivery strategies to enhance their safety and efficacy. Here, we provide an overview of the current clinically relevant RNA therapeutics, mechanistic basis of their function, and strategies to improve their clinical use. We discuss the 17 approved RNA therapeutics and perform an in-depth analysis of the 222 ongoing clinical trials, with an emphasis on their respective mechanisms and disease areas. We also provide perspectives on the challenges for clinical translation of RNA therapeutics and suggest potential strategies to address these challenges.

Keywords: RNA therapeutic; antisense oligonucleotide; aptamer; clinical trial; gene therapy; lipid nanoparticle; mRNA; mRNA vaccine; siRNA.

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Figures

FIGURE 1
FIGURE 1
Summary of RNA therapeutic ongoing clinical trial landscape with a schematic representation of the mechanisms of action involved in different classes of RNA therapeutics. Created with BioRender.com
FIGURE 2
FIGURE 2
Landscape of RNA therapeutics with 222 ongoing clinical trials. The trials were further analyzed based on (a) RNA type, (b) phase, (c) prior approval status, (d) disease type, (e) administration route, and (f) delivery system
FIGURE 3
FIGURE 3
Landscape of 118 ongoing mRNA therapeutic clinical trials. The trials were analyzed based on (a) disease type, (b) administration route, and (c) delivery System
FIGURE 4
FIGURE 4
Landscape of 38 ongoing mRNA therapeutic clinical trials that are not for COVID‐19 vaccines. The trials were further analyzed based on (a) phase, (b) disease type, (c) administration route, and (d) delivery system
FIGURE 5
FIGURE 5
Landscape of 44 ongoing ASO therapeutic clinical trials. The trials were analyzed based on (a) disease type, (b) administration route, and (c) delivery system
FIGURE 6
FIGURE 6
Landscape of 54 ongoing siRNA therapeutic clinical trials. The trials were analyzed based on (a) disease type, (b) administration route, and (c) delivery system
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