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

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.