The steady progress in genome editing, especially genome editing based on the use of clustered regularly interspaced short palindromic repeats (CRISPR) and programmable nucleases to make precise modifications to genetic material, has provided enormous opportunities to advance biomedical research and promote human health. However, limited transfection efficiency of CRISPR-Cas9 poses a substantial challenge, hindering its wide adoption for genetic modification. Recent advancements in nanoparticle technology, specifically lipid nanoparticles (LNPs), offer promising opportunities for targeted drug delivery. LNPs are becoming popular as a means of delivering therapeutics, including those based on nucleic acids and mRNA. Notably, certain LNPs, such as Polyethylene glycol-phospholipid-modified cationic lipid nanoparticles and solid lipid nanoparticles, exhibit remarkable potential for efficient CRISPR-Cas9 delivery as a gene editing instrument. This review will introduce the molecular mechanisms and diverse applications of the CRISPR/Cas9 gene editing system, current strategies for delivering CRISPR/Cas9-based tools, the advantage of LNPs for CRISPR-Cas9 delivery, an overview of strategies for overcoming off-target genome editing, and approaches for improving genome targeting and tissue targeting. We will also highlight current developments and recent clinical trials for the delivery of CRISPR/Cas9. Finally, future directions for overcoming the limitations and adaptation of this technology for clinical trials will be discussed.
Keywords: CRISPR-Cas9; Drug delivery; Genome editing; Lipid nanoparticles.
© 2024 The Authors. Published by Elsevier Ltd.