Nanoparticles-mediated CRISPR/Cas9 delivery: Recent advances in cancer treatment

Abstract

Clustered regularly interspaced short palindromic repeat-CRISPR-associated protein (CRISPR-Cas) genome-editing systems, prokaryotic adaptive immune system, have been exploited and prepared a robust programmable method for efficient and accurate genome editing and gene targeting. This revolutionary technique can be used for engineered cell therapies, in vivo gene therapy, animal modeling, and cancer diagnosis and treatment. Recently, safe and efficient delivery is one of the greatest challenges in the clinical utilization of CRISPR/Cas9. Though using viral delivery strategies have many advantages for both in vitro and in vivo genome editing, their severe impediments like small insertion size, high carcinogenesis risk, and immune system stimulation, cause many problems for both laboratory and clinical applications. Consequently, there is a critical need for the development of novel non-viral delivery systems such as physical delivery and nanoparticle-based delivery. To date, the nanoparticle-based delivery strategy has attracted great attention because of their tremendous potential for combination therapies, large insertion size, easy large-scale production, and efficient in vivo application. Here, we review the current advances in nanoparticle-mediated CRISPR/Cas9 delivery platforms like polymeric- and lipid-based structures, rigid nanoparticles, nanoparticles coupled to specific ligand systems including arginine–glycine–aspartate (RGD) peptide, TAT peptide, aptamers, and cell-penetrating peptides (CPP), and more important, smart DNA nanostructures. Furthermore, the application of CRISPR/Cas9 systems-based nanoparticle delivery strategy to increase the potency and safety of immunotherapy-based drugs as a favorable future cancer treatment is proposed.