Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Clinical Outlook
  • Published:

PCSK9-targeted therapies: present and future approaches

Nature Reviews Cardiology volume 18, pages 805–806 (2021)Cite this article

Subjects

Human genetic studies combined with biotechnological advances have guided and accelerated the development of PCSK9-targeting therapies. In this Clinical Outlook, we highlight present and future approaches for PCSK9 inhibition to reduce LDL-cholesterol levels and the risk of atherosclerotic cardiovascular disease.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Therapeutic strategies to target PCSK9.

References

  1. Cohen, J. C., Boerwinkle, E., Mosley, T. H. Jr & Hobbs, H. H. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N. Engl. J. Med. 354, 1264–1272 (2006).

    Article  CAS  Google Scholar 

  2. Sabatine, M. S. et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N. Engl. J. Med. 376, 1713–1722 (2017).

    Article  CAS  Google Scholar 

  3. Schwartz, G. G. et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N. Engl. J. Med. 379, 2097–2107 (2018).

    Article  CAS  Google Scholar 

  4. Ridker, P. M. et al. Cardiovascular efficacy and safety of bococizumab in high-risk patients. N. Engl. J. Med. 376, 1527–1539 (2017).

    Article  CAS  Google Scholar 

  5. Ray, K. K. et al. Two phase 3 trials of inclisiran in patients with elevated LDL cholesterol. N. Engl. J. Med. 382, 1507–1519 (2020).

    Article  CAS  Google Scholar 

  6. Gennemark, P. et al. An oral antisense oligonucleotide for PCSK9 inhibition. Sci. Transl Med. 13, eabe9117 (2021).

    Article  CAS  Google Scholar 

  7. Alleyne, C. et al. Series of novel and highly potent cyclic peptide PCSK9 inhibitors derived from an mRNA display screen and optimized via structure-based design. J. Med. Chem. 63, 13796–13824 (2020).

    Article  CAS  Google Scholar 

  8. Momtazi-Borojeni, A. A. et al. Pre-clinical evaluation of the nanoliposomal antiPCSK9 vaccine in healthy non-human primates. Vaccines 9, 749 (2021).

    Article  CAS  Google Scholar 

  9. Musunuru, K. et al. In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates. Nature 593, 429–434 (2021).

    Article  CAS  Google Scholar 

  10. Rothgangl, T. et al. In vivo adenine base editing of PCSK9 in macaques reduces LDL cholesterol levels. Nat. Biotechnol. 39, 949–957 (2021).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Section of Cardiology, Baylor College of Medicine, Houston, TX, USA

    Mahmoud Al Rifai & Christie M. Ballantyne

Authors
  1. Mahmoud Al Rifai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christie M. Ballantyne
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christie M. Ballantyne.

Ethics declarations

Competing interests

C.M.B. has received grant/research support (to his institution) from Abbott Diagnostics, Akcea, Amgen, Esperion, Ionis, Novartis, Regeneron and Roche Diagnostic, and has been a consultant for Abbott Diagnostics, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Corvidia, Denka Seiken, Esperion, Genentech, Gilead, Matinas BioPharma, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, Roche Diagnostic and Sanofi-Synthelabo. M.A.R. declares no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rifai, M.A., Ballantyne, C.M. PCSK9-targeted therapies: present and future approaches. Nat Rev Cardiol 18, 805–806 (2021). https://doi.org/10.1038/s41569-021-00634-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41569-021-00634-0

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research