Functional peptide-assisted delivery of CRISPR/Cas9: Recent progress on gene editing

Abstract

The CRISPR/Cas9 system has transformed the field of genome engineering by enabling precise and programmable modification of genomic sequences. Despite its remarkable potential, efficient and safe delivery of CRISPR/Cas9 components remains a significant bottleneck, particularly in translational and therapeutic applications. In the past decade (2015-2025), peptide-based delivery systems have gained increasing attention as versatile non-viral alternatives due to their modular design, inherent biocompatibility and potential for tissue-specific targeting. This review provides a critical synthesis of recent advances in functional peptide-based delivery strategies for CRISPR/Cas9. We focus on key categories of peptides—cell-penetrating peptides, cell-targeting peptides, endosomal escape peptides, and nuclear localization signals—and their multifunctional or hybrid combinations. By identifying key design principles and failure modes, this review discusses how these platforms can be optimized to support the development of next-generation CRISPR therapeutics, ultimately moving closer to safe and effective genome editing in future clinical applications.