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Gene Therapy Targeting PCSK9
The last decades of research in cardiovascular prevention have been characterized by successful bench-to-bedside developments for the treatment of low-density lipoprotein (LDL) hypercholesterolemia. Recent examples include the inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) with...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8781734/ https://www.ncbi.nlm.nih.gov/pubmed/35050192 http://dx.doi.org/10.3390/metabo12010070 |
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author | Katzmann, Julius L. Cupido, Arjen J. Laufs, Ulrich |
author_facet | Katzmann, Julius L. Cupido, Arjen J. Laufs, Ulrich |
author_sort | Katzmann, Julius L. |
collection | PubMed |
description | The last decades of research in cardiovascular prevention have been characterized by successful bench-to-bedside developments for the treatment of low-density lipoprotein (LDL) hypercholesterolemia. Recent examples include the inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) with monoclonal antibodies, small interfering RNA and antisense RNA drugs. The cumulative effects of LDL cholesterol on atherosclerosis make early, potent, and long-term reductions in LDL cholesterol desirable—ideally without the need of regular intake or application of medication and importantly, without side effects. Current reports show durable LDL cholesterol reductions in primates following one single treatment with PCSK9 gene or base editors. Use of the CRISPR/Cas system enables precise genome editing down to single-nucleotide changes. Provided safety and documentation of a reduction in cardiovascular events, this novel technique has the potential to fundamentally change our current concepts of cardiovascular prevention. In this review, the application of the CRISPR/Cas system is explained and the current state of in vivo approaches of PCSK9 editing is presented. |
format | Online Article Text |
id | pubmed-8781734 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87817342022-01-22 Gene Therapy Targeting PCSK9 Katzmann, Julius L. Cupido, Arjen J. Laufs, Ulrich Metabolites Review The last decades of research in cardiovascular prevention have been characterized by successful bench-to-bedside developments for the treatment of low-density lipoprotein (LDL) hypercholesterolemia. Recent examples include the inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) with monoclonal antibodies, small interfering RNA and antisense RNA drugs. The cumulative effects of LDL cholesterol on atherosclerosis make early, potent, and long-term reductions in LDL cholesterol desirable—ideally without the need of regular intake or application of medication and importantly, without side effects. Current reports show durable LDL cholesterol reductions in primates following one single treatment with PCSK9 gene or base editors. Use of the CRISPR/Cas system enables precise genome editing down to single-nucleotide changes. Provided safety and documentation of a reduction in cardiovascular events, this novel technique has the potential to fundamentally change our current concepts of cardiovascular prevention. In this review, the application of the CRISPR/Cas system is explained and the current state of in vivo approaches of PCSK9 editing is presented. MDPI 2022-01-12 /pmc/articles/PMC8781734/ /pubmed/35050192 http://dx.doi.org/10.3390/metabo12010070 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Katzmann, Julius L. Cupido, Arjen J. Laufs, Ulrich Gene Therapy Targeting PCSK9 |
title | Gene Therapy Targeting PCSK9 |
title_full | Gene Therapy Targeting PCSK9 |
title_fullStr | Gene Therapy Targeting PCSK9 |
title_full_unstemmed | Gene Therapy Targeting PCSK9 |
title_short | Gene Therapy Targeting PCSK9 |
title_sort | gene therapy targeting pcsk9 |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8781734/ https://www.ncbi.nlm.nih.gov/pubmed/35050192 http://dx.doi.org/10.3390/metabo12010070 |
work_keys_str_mv | AT katzmannjuliusl genetherapytargetingpcsk9 AT cupidoarjenj genetherapytargetingpcsk9 AT laufsulrich genetherapytargetingpcsk9 |