Gene therapy requires safe and effective vectors to deliver genes to their target
site of action. Non-viral gene delivery systems have attracted growing attention due to their
low toxicity, low immunogenicity and ease of production compared to viral vectors. Most
non-viral gene delivery systems enter cells via endocytic pathways, and their escape from
endosomes is therefore crucial for successful transfection. Several reagents have been developed to promote
endosomal escape, including peptides, polymers and lipids. Among these, endosome-disrupting peptides have
been used in many studies, and have proven to be one of the most promising approaches to overcome endosomal
entrapment and lysosomal degradation. This review provides an up-to-date summary of strategies for
enhancing endosomal escape, with a focus on the modification of endosome-disrupting peptides to further increase
the efficient delivery of oligonucleotides.
Keywords: Endosome escape, fusogenic peptides, gene delivery, non-viral vectors, oligonucleotides, peptides.
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