Current and prospective strategies for advancing the targeted delivery of CRISPR/Cas system via extracellular vesicles

Extracellular vesicles (EVs) have emerged as a promising platform for gene delivery owing to their natural properties and phenomenal functions, being able to circumvent the significant challenges associated with toxicity, problematic biocompatibility, and immunogenicity of the standard approaches. These features are of particularly interest for targeted delivery of the emerging clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) systems. However, the current efficiency of EV-meditated transport of CRISPR/Cas components remains insufficient due to numerous exogenous and endogenous barriers. Here, we comprehensively reviewed the current status of EV-based CRISPR/Cas delivery systems. In particular, we explored various strategies and methodologies available to potentially improve the loading capacity, safety, stability, targeting, and tracking for EV-based CRISPR/Cas system delivery. Additionally, we hypothesise the future avenues for the development of EV-based delivery systems that could pave the way for novel clinically valuable gene delivery approaches, and may potentially bridge the gap between gene editing technologies and the laboratory/clinical application of gene therapies.

Automated summary

Extracellular vesicles (EVs) show promise as a gene delivery platform for targeted CRISPR/Cas systems, overcoming challenges associated with toxicity and immunogenicity. This review explores strategies to improve loading capacity, safety, stability, targeting, and tracking for EV-based CRISPR/Cas delivery. It hypothesizes future avenues for EV-based delivery systems to bridge the gap between gene editing technologies and gene therapies.