Liposomes are one of the most widely investigated carriers for CRISPR/Cas9 delivery. The surface properties of liposomal carriers, including the surface charge, PEGylation, and ligand modification can significantly affect the gene silencing efficiency. Three barriers of systemic CRISPR/Cas9 delivery (long blood circulation, efficient tumor penetration, and efficient cellular uptake/endosomal escape) are analyzed on liposomal carriers with different surface charges, PEGylations, and ligand modifications. Cationic formulations dominate CRISPR/Cas9 delivery and neutral formulations also have good performance while anionic formulations are generally not proper for CRISPR/Cas9 delivery. The PEG dilemma (prolonged blood circulation vs. reduced cellular uptake/endosomal escape) and the side effect of repeated PEGylated formulation (accelerated blood clearance) were discussed. Effects of ligand modification on cationic and neutral formulations were analyzed. Finally, we summarized the achievements in liposomal CRISPR/Cas9 delivery, outlined existing problems, and provided some future perspectives. Liposomes are one of the most widely investigated carriers for CRISPR/Cas9 delivery. The surface properties of liposomal carriers, including the surface charge, PEGylation, and ligand modification can significantly affect the gene silencing efficiency. Three barriers of systemic siRNA delivery (long blood circulation, efficient tumor penetration, and efficient cellular uptake/endosomal escape) are analyzed on liposomal carriers with different surface charges, PEGylations, and ligand modifications. Cationic formulations dominate CRISPR/Cas9 delivery and neutral formulations also have good performance while anionic formulations are generally not proper for CRISPR/Cas9 delivery. The PEG dilemma (prolonged blood circulation vs. reduced cellular uptake/endosomal escape) and the side effect of repeated PEGylated formulation (accelerated blood clearance) were discussed. Effects of ligand modification on cationic and neutral formulations were analyzed. Finally, we summarized the achievements in liposomal CRISPR/Cas9 delivery, outlined existing problems, and provided some future perspectives.
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