Targeting RNA With Antisense Oligonucleotides and Small Interfering RNA JACC State-of-the-Art Review

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

卷:76

Review

Katzmann, Julius L.¹  Packard, Chris J.²  Chapman, M. John^3,4  Katzmann, Isabell⁵  Laufs, Ulrich¹ 

[1] Univ Hosp Leipzig, Dept Cardiol, Leipzig, Germany

[2] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland

[3] Sorbonne Univ, Pitie Salpetriere Univ Hosp, Endocrinol Metab Div, Paris, France

[4] Natl Inst Hlth & Med Res INSERM, Paris, France

[5] Zeisigwaldkliniken Bethanien Chemnitz, Dept Internal Med, Chemnitz, Germany

关键词: angiopoietin-like 3;    apolipoprotein CIII;    ASO;    lipoprotein(a);    PCSK9;    siRNA;   

DOI  :  10.1016/j.jacc.2020.05.070

来源: Elsevier

【 摘 要 】

There is an unmet clinical need to reduce residual cardiovascular risk attributable to apolipoprotein B-containing lipo-proteins, particularly low-density lipoprotein and remnant particles. Pharmacological targeting of messenger RNA rep-resents an emerging, innovative approach. Two major classes of agents have been developed-antisense oligonucleotides and small interfering RNA. Early problems with their use have been overcome by conjugation with N-acetylgalactos-amine, an adduct that targets their delivery to the primary site of action in the liver. Using these agents to inhibit the translation of key regulatory proteins such as PCSK9, apolipoprotein CIII, apolipoprotein(a), and angiopoietin-like 3 has been shown to be effective in attenuating dyslipidemic states. Cardiovascular outcome trials with N-acetylgalactos-amine-conjugated RNA-targeting drugs are ongoing. The advantages of these agents include long dosing intervals of up to 6 months and the potential to regulate the abundance of any disease-related protein. Long-term safety has yet to be demonstrated in large-scale clinical trials. (c) 2020 by the American College of Cardiology Foundation.

【 授权许可】

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