RNA interference in the era of nucleic acid therapeutics

被引：98

作者：

Jadhav, Vasant ^{[1
]}

Vaishnaw, Akshay ^{[1
]}

Fitzgerald, Kevin ^{[1
]}

Maier, Martin A. ^{[1
]}

机构：

[1] Alnylam Pharmaceut, Res & Dev, Cambridge, MA 02142 USA

来源：

NATURE BIOTECHNOLOGY | 2024年 / 42卷 / 3期

关键词：

DOUBLE-STRANDED-RNA; MESSENGER-RNA; IN-VIVO; LIPID NANOPARTICLES; MAMMALIAN MICRORNAS; SYSTEMIC DELIVERY; CATIONIC LIPIDS; GENE; OLIGONUCLEOTIDE; CHOLESTEROL;

D O I：

10.1038/s41587-023-02105-y

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Two decades of research on RNA interference (RNAi) have transformed a breakthrough discovery in biology into a robust platform for a new class of medicines that modulate mRNA expression. Here we provide an overview of the trajectory of small-interfering RNA (siRNA) drug development, including the first approval in 2018 of a liver-targeted siRNA interference (RNAi) therapeutic in lipid nanoparticles and subsequent approvals of five more RNAi drugs, which used metabolically stable siRNAs combined with N-acetylgalactosamine ligands for conjugate-based liver delivery. We also consider the remaining challenges in the field, such as delivery to muscle, brain and other extrahepatic organs. Today's RNAi therapeutics exhibit high specificity, potency and durability, and are transitioning from applications in rare diseases to widespread, chronic conditions. With six approved drugs, siRNA is now an established therapeutic modality poised for expansion.

引用

页码：394 / 405

页数：12

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