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Ribonucleic acid and gene therapies in cardiovascular disease: clinical applications, delivery challenges and emerging precision tools

Title: Ribonucleic acid and gene therapies in cardiovascular disease: clinical applications, delivery challenges and emerging precision tools
Authors: Jordan, Alex J; Balmforth, Craig; Craig, Neil; Dhaun, Neeraj; Baker, Andrew; Dweck, Marc Richard; Newby, David E
Contributors: Association of Medical Research Charities
Source: Heart ; page heartjnl-2024-325280 ; ISSN 1355-6037 1468-201X
Publisher Information: BMJ
Publication Year: 2025
Description: Cardiovascular diseases remain a leading cause of global mortality despite advancements in pharmacotherapies, with current treatments facing challenges related to efficacy, tolerability and patient adherence. In response, advanced therapies, such as RNA and gene therapies, have emerged as a promising alternative for addressing both acquired and monogenic cardiovascular conditions. This review explores the current landscape of RNA and gene therapies for cardiovascular disease, focusing on RNA-based therapeutics such as small-interfering RNAs (siRNAs), antisense oligonucleotides and clustered regularly interspaced short palindromic repeats and associated Cas9 endonuclease (CRISPR-Cas9)-based gene editing systems. Recent European Medicines Agency and Food and Drug Administration-approved RNA therapies, including patisiran, vutrisiran and inclisiran, which employ lipid nanoparticle delivery systems, highlight the clinical potential of siRNAs for targeting hepatic molecular pathways. Emerging CRISPR-Cas9 technologies are poised to address genetic mutations at their source, offering permanent correction of pathogenic variants and the potential to treat a broad range of hereditary cardiovascular conditions. Together, these therapies represent a major leap forward in precision medicine, offering long-lasting therapeutic effects and improved patient care and adherence. However, many challenges remain, particularly in targeting such therapies to cardiac tissues and optimising delivery systems. This review discusses the current state of the art in cardiovascular RNA and gene therapies, including current evidence, delivery challenges and the current landscape of gene and RNA therapies in phase I clinical trials and beyond.
Document Type: article in journal/newspaper
Language: English
DOI: 10.1136/heartjnl-2024-325280
Availability: https://doi.org/10.1136/heartjnl-2024-325280; https://syndication.highwire.org/content/doi/10.1136/heartjnl-2024-325280
Accession Number: edsbas.A70DD251
Database: BASE