Recent advances in delivery strategies for CRISPR-based genome editing

Abstract The rapid development of CRISPR genome editing technologies has established a transformative paradigm within biomedical research, drug discovery, and gene therapy. Despite the robust nuclease activity and programmable targeting exhibited by these systems, the clinical translation of CRISPR-mediated therapeutics remains substantially impeded by systemic and cellular delivery constraints. Specifically, the secure, highly efficient, and spatiotemporally controlled administration of CRISPR machinery to designated tissues or distinct cell populations constitutes the primary bottleneck in the field. Physiological and biological impediments, including rapid clearance, limited tissue penetration, endosomal entrapment, and potential adaptive immune responses, necessitate the development of highly specialized delivery vectors to ensure therapeutic viability and mitigate off-target effects. To circumvent these biological barriers, contemporary research has extensively evaluated a spectrum of delivery vehicles engineered to package and protect diverse CRISPR cargoes, including DNA, RNA, and pre-assembled ribonucleoprotein complexes. These diverse cargos are actively investigated in conjunction with established viral vectors, and an expanding array of non-viral vectors encompassing physical methods, nanoparticle‑based systems, and peptide/protein‑mediated platforms. This review delineates the recent advancements in discovery of CRISPR‑based genome editing tools, with a particular emphasis on delivery strategies across in vitro modeling, ex vivo cellular engineering, and in vivo clinical interventions.