Lipid nanoparticle (LNP) mediated mRNA delivery in cardiovascular diseases: Advances in genome editing and CAR T cell therapy

🥉 Top 5% JournalJun 14, 2024Journal of controlled release : official journal of the Controlled Release Society

Using lipid nanoparticles to deliver mRNA for gene editing and CAR T cell treatments in heart diseases

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Abstract

Cardiovascular diseases (CVDs) account for the leading cause of global mortality among non-communicable diseases.

Current cardiac regeneration treatments have limitations and may lead to adverse reactions.
Messenger RNA (mRNA) shows potential as a therapeutic agent due to its ability to encode proteins and target difficult conditions.
mRNA offers low toxicity and high efficiency in delivering proteins without altering the genome.
Challenges for mRNA include immunogenicity, instability, and issues with entering cells, which can impede its clinical use.
Lipid nanoparticles (LNPs) are emerging as effective delivery systems for mRNA, particularly in the context of CVDs.
Advanced technologies, including artificial intelligence, may improve the design and formulation of mRNA-LNP therapies.

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Cardiovascular diseases (CVDs) are the leading cause of global mortality among non-communicable diseases. Current cardiac regeneration treatments have limitations and may lead to adverse reactions. Hence, innovative technologies are needed to address these shortcomings. Messenger RNA (mRNA) emerges as a promising therapeutic agent due to its versatility in encoding therapeutic proteins and targeting "undruggable" conditions. It offers low toxicity, high transfection efficiency, and controlled protein production without genome insertion or mutagenesis risk. However, mRNA faces challenges such as immunogenicity, instability, and difficulty in cellular entry and endosomal escape, hindering its clinical application. To overcome these hurdles, lipid nanoparticles (LNPs), notably used in COVID-19 vaccines, have a great potential to deliver mRNA therapeutics for CVDs. This review highlights recent progress in mRNA-LNP therapies for CVDs, including Myocardial Infarction (MI), Heart Failure (HF), and hypercholesterolemia. In addition, LNP-mediated mRNA delivery for CAR T-cell therapy and CRISPR/Cas genome editing in CVDs and the related clinical trials are explored. To enhance the efficiency, safety, and clinical translation of mRNA-LNPs, advanced technologies like artificial intelligence (AGILE platform) in RNA structure design, and optimization of LNP formulation could be integrated. We conclude that the strategies to facilitate the extra-hepatic delivery and targeted organ tropism of mRNA-LNPs (SORT, ASSET, SMRT, and barcoded LNPs) hold great prospects to accelerate the development and translation of mRNA-LNPs in CVD treatment.

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