Delivery of nucleic acid based genome editing platforms via lipid nanoparticles: Clinical applications

Razan Masarwy, Lior Stotsky-Oterin, Aviad Elisha, Inbal Hazan-Halevy*, Dan Peer

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

CRISPR/Cas technology presents a promising approach for treating a wide range of diseases, including cancer and genetic disorders. Despite its potential, the translation of CRISPR/Cas into effective in-vivo gene therapy encounters challenges, primarily due to the need for safe and efficient delivery mechanisms. Lipid nanoparticles (LNPs), FDA-approved for RNA delivery, show potential for delivering also CRISPR/Cas, offering the capability to efficiently encapsulate large mRNA molecules with single guide RNAs. However, achieving precise targeting in-vivo remains a significant obstacle, necessitating further research into optimizing LNP formulations. Strategies to enhance specificity, such as modifying LNP structures and incorporating targeting ligands, are explored to improve organ and cell type targeting. Furthermore, the development of base and prime editing technology presents a potential breakthrough, offering precise modifications without generating double-strand breaks (DSBs). Prime editing, particularly when delivered via targeted LNPs, holds promise for treating diverse diseases safely and precisely. This review assesses both the progress made and the persistent challenges faced in using LNP-encapsulated CRISPR-based technologies for therapeutic purposes, with a particular focus on clinical translation.

Original languageEnglish
Article number115359
JournalAdvanced Drug Delivery Reviews
Volume211
DOIs
StatePublished - Aug 2024

Funding

FundersFunder number
ART Biosciences
SirTLabs Corporation
Teva Pharmaceutical Industries
Earli Inc.
European Union ’s Horizon 2020 Research and Innovation Programme
Roche
Tel Aviv University
Lewis Trust for Blood Cancer
European Research Council101055029
European Research Council
Horizon 2020825828
Horizon 2020
Israel Science Foundation2012/20
Israel Science Foundation

    Keywords

    • Base editor
    • CRISPR Cas9
    • Gene editing
    • Genetic Medicines
    • Lipid nanoparticles
    • Prime editor

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