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Inclisiran—Safety and Effectiveness of Small Interfering RNA in Inhibition of PCSK-9

Dyslipidemia is listed among important cardiovascular disease risk factors. Treating lipid disorders is difficult, and achieving desirable levels of LDL-cholesterol (LDL-C) is essential in both the secondary and primary prevention of cardiovascular disease. For many years, statins became the basis o...

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Autores principales: Wołowiec, Łukasz, Osiak, Joanna, Wołowiec, Anna, Wijata, Aleksandra, Grześk, Elżbieta, Kozakiewicz, Mariusz, Banach, Joanna, Nowaczyk, Alicja, Nowaczyk, Jacek, Grześk, Grzegorz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9965021/
https://www.ncbi.nlm.nih.gov/pubmed/36839644
http://dx.doi.org/10.3390/pharmaceutics15020323
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author Wołowiec, Łukasz
Osiak, Joanna
Wołowiec, Anna
Wijata, Aleksandra
Grześk, Elżbieta
Kozakiewicz, Mariusz
Banach, Joanna
Nowaczyk, Alicja
Nowaczyk, Jacek
Grześk, Grzegorz
author_facet Wołowiec, Łukasz
Osiak, Joanna
Wołowiec, Anna
Wijata, Aleksandra
Grześk, Elżbieta
Kozakiewicz, Mariusz
Banach, Joanna
Nowaczyk, Alicja
Nowaczyk, Jacek
Grześk, Grzegorz
author_sort Wołowiec, Łukasz
collection PubMed
description Dyslipidemia is listed among important cardiovascular disease risk factors. Treating lipid disorders is difficult, and achieving desirable levels of LDL-cholesterol (LDL-C) is essential in both the secondary and primary prevention of cardiovascular disease. For many years, statins became the basis of lipid-lowering therapy. Nevertheless, these drugs are often insufficient due to their side effects and restrictive criteria for achieving the recommended LDL-C values. Even the addition of other drugs, i.e., ezetimibe, does not help one achieve the target LDL-C. The discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9) discovery has triggered intensive research on a new class of protein-based drugs. The protein PCSK9 is located mainly in hepatocytes and is involved in the metabolism of LDL-C. In the beginning, antibodies against the PCSK9 protein, such as evolocumab, were invented. The next step was inclisiran. Inclisiran is a small interfering RNA (siRNA) that inhibits the expression of PCSK9 by binding specifically to the mRNA precursor of PCSK9 protein and causing its degradation. It has been noticed in recent years that siRNA is a powerful tool for biomedical research and drug discovery. The purpose of this work is to summarize the molecular mechanisms, pharmacokinetics, pharmacodynamics of inclisiran and to review the latest research.
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spelling pubmed-99650212023-02-26 Inclisiran—Safety and Effectiveness of Small Interfering RNA in Inhibition of PCSK-9 Wołowiec, Łukasz Osiak, Joanna Wołowiec, Anna Wijata, Aleksandra Grześk, Elżbieta Kozakiewicz, Mariusz Banach, Joanna Nowaczyk, Alicja Nowaczyk, Jacek Grześk, Grzegorz Pharmaceutics Review Dyslipidemia is listed among important cardiovascular disease risk factors. Treating lipid disorders is difficult, and achieving desirable levels of LDL-cholesterol (LDL-C) is essential in both the secondary and primary prevention of cardiovascular disease. For many years, statins became the basis of lipid-lowering therapy. Nevertheless, these drugs are often insufficient due to their side effects and restrictive criteria for achieving the recommended LDL-C values. Even the addition of other drugs, i.e., ezetimibe, does not help one achieve the target LDL-C. The discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9) discovery has triggered intensive research on a new class of protein-based drugs. The protein PCSK9 is located mainly in hepatocytes and is involved in the metabolism of LDL-C. In the beginning, antibodies against the PCSK9 protein, such as evolocumab, were invented. The next step was inclisiran. Inclisiran is a small interfering RNA (siRNA) that inhibits the expression of PCSK9 by binding specifically to the mRNA precursor of PCSK9 protein and causing its degradation. It has been noticed in recent years that siRNA is a powerful tool for biomedical research and drug discovery. The purpose of this work is to summarize the molecular mechanisms, pharmacokinetics, pharmacodynamics of inclisiran and to review the latest research. MDPI 2023-01-18 /pmc/articles/PMC9965021/ /pubmed/36839644 http://dx.doi.org/10.3390/pharmaceutics15020323 Text en © 2023 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
Wołowiec, Łukasz
Osiak, Joanna
Wołowiec, Anna
Wijata, Aleksandra
Grześk, Elżbieta
Kozakiewicz, Mariusz
Banach, Joanna
Nowaczyk, Alicja
Nowaczyk, Jacek
Grześk, Grzegorz
Inclisiran—Safety and Effectiveness of Small Interfering RNA in Inhibition of PCSK-9
title Inclisiran—Safety and Effectiveness of Small Interfering RNA in Inhibition of PCSK-9
title_full Inclisiran—Safety and Effectiveness of Small Interfering RNA in Inhibition of PCSK-9
title_fullStr Inclisiran—Safety and Effectiveness of Small Interfering RNA in Inhibition of PCSK-9
title_full_unstemmed Inclisiran—Safety and Effectiveness of Small Interfering RNA in Inhibition of PCSK-9
title_short Inclisiran—Safety and Effectiveness of Small Interfering RNA in Inhibition of PCSK-9
title_sort inclisiran—safety and effectiveness of small interfering rna in inhibition of pcsk-9
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9965021/
https://www.ncbi.nlm.nih.gov/pubmed/36839644
http://dx.doi.org/10.3390/pharmaceutics15020323
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