Redox-Responsive Systems in Gene Editing and CRISPR-Cas9 Delivery

Lustrous, regularly interspaced short palindromic repeat (CRISPR)–associated protein 9 (Cas9) is a potential gene-editing method for treating genetic illnesses. Nonetheless, the problem of safely and efficiently delivering CRISPR/Cas9 to host cells limits its clinical use. Intracellular redox-triggered release properties are used to encapsulate and deliver all three types of CRISPR-Cas9 editing machinery, namely pDNA, mRNA/sgRNA, and the ribonucleoprotein complex, advancing CRISPR/Cas9-based delivery strategies and facilitating breakthroughs in biomedical research and therapeutics. CRISPR/Cas9 has revolutionized genome editing by allowing for precise and efficient genetic alterations in a variety of biological systems. Despite its rising therapeutic promise, major problems remain in decreasing off-target effects, reducing immunogenicity, and optimizing CRISPR component transport into target cells, emphasizing recent breakthroughs in the utilization of polymeric carriers, hybrid platforms, and lipid nanoparticles. We also focus on a frequently ignored factor: the Cas9 protein’s aggregation behavior. The future of CRISPR/Cas9 gene therapy is dependent on the development of improved and specialized delivery technologies, as well as the improvement of genome editing precision. Recent breakthroughs in nanotechnology, notably the use of LNPs, polymeric carriers, and other nonviral vectors, have improved the safety and effectiveness of CRISPR/Cas9 delivery systems.