New Approaches for Targeting PCSK9: Small-Interfering Ribonucleic Acid and Genome Editing

Arteriosclerosis, Thrombosis, and Vascular Biology - Tập 43 Số 7 - Trang 1081-1092 - 2023
Reindert F. Oostveen1, Amit V. Khera2, Sekar Kathiresan3, Erik S.G. Stroes4, Kevin Fitzgerald5, Matthew J. Harms6, Benjamin L. Oakes7, John J.P. Kastelein8
1Reindert F. Oostveen https://orcid.org/0000-0001-7182-2886 Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, The Netherlands (R.F.O., E.S.G.S., J.J.P.K.).
2Amit V. Khera https://orcid.org/0000-0001-6535-5839 Verve Therapeutics, Boston, MA (A.V.K., S.K.).
3Sekar Kathiresan https://orcid.org/0000-0002-3711-7101 Verve Therapeutics, Boston, MA (A.V.K., S.K.).
4Erik S.G. Stroes https://orcid.org/0000-0001-9555-6260 Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, The Netherlands (R.F.O., E.S.G.S., J.J.P.K.).
5Kevin Fitzgerald Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, The Netherlands (R.F.O., E.S.G.S., J.J.P.K.).
6Matthew J. Harms Scribe Therapeutics, Alameda, CA (M.J.H., B.L.O.).
7Benjamin L. Oakes Scribe Therapeutics, Alameda, CA (M.J.H., B.L.O.).
8Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, The Netherlands (R.F.O., E.S.G.S., J.J.P.K.).

Tóm tắt

There is overwhelming clinical and genetic evidence supporting the concept that low-density-lipoprotein cholesterol should be as low as possible for as long as possible in patients at very high cardiovascular risk. Despite the wide availability of effective lipid-lowering therapies, the majority of patients still fail to reach guideline-based lipid goals. Advances in novel approaches targeting PCSK9 (proprotein convertase subtilisin/kexin type 9) through small-interfering RNA and genome editing hold the potential to bridge this gap, by offering long-acting alternatives, which may overcome adherence and other challenges in the current chronic care model. In this review, we discuss the history of targeting PCSK9 with the use of mRNA and small-interfering ribonucleic acid. We also shed light on targeting PCSK9 with genome editing, including discussion of the VERVE-101 clustered regularly interspaced short palindromic repeats-base editing medicine currently being evaluated in a clinical trial and others in development.

Từ khóa


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Arteriosclerosis, Thrombosis, and Vascular Biology

Tập 43 Số 7

1081-1092

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