Delivery of CRISPR/Cas9 for therapeutic genome editing

Abstract

The clustered, regularly‐interspaced, short palindromic repeat (CRISPR)‐associated nuclease 9 (CRISPR/Cas9) is emerging as a promising genome‐editing tool for treating diseases in a precise way, and has been applied to a wide range of research in the areas of biology, genetics, and medicine. Delivery of therapeutic genome‐editing agents provides a promising platform for the treatment of genetic disorders. Although viral vectors are widely used to deliver CRISPR/Cas9 elements with high efficiency, they suffer from several drawbacks, such as mutagenesis, immunogenicity, and off‐target effects. Recently, non‐viral vectors have emerged as another class of delivery carriers in terms of their safety, simplicity, and flexibility. In this review, we discuss the modes of CRISPR/Cas9 delivery, the barriers to the delivery process and the application of CRISPR/Cas9 system for the treatment of genetic disorders. We also highlight several representative types of non‐viral vectors, including polymers, liposomes, cell‐penetrating peptides, and other synthetic vectors, for the therapeutic delivery of CRISPR/Cas9 system. The applications of CRISPR/Cas9 in treating genetic disorders mediated by the non‐viral vectors are also discussed.

Aptamer/Peptide‐Functionalized Genome‐Editing System for Effective Immune Restoration through Reversal of PD‐L1‐Mediated Cancer Immunosuppression

“…Non‐viral vectors with a better safety profile usually do not possess sufficient transfection efficiency. [ 7–12 ] The reported non‐viral vectors cover diverse materials such as lipid‐like materials, [ 13,14 ] cell exosomes, [ 15 ] polymers and their hybrids, [ 16–22 ] nucleic acid based materials, [ 23 ] and metal containing materials. [ 24–26 ] Nevertheless, in spite of extensive studies on functionalization of non‐viral vectors, the studies on the vectors for delivery of genome editing plasmids are relatively rare.…”

“…To realize safe delivery of CRISPR‐Cas9 plasmids into targeted tumor cells with a high efficiency is still challenging. [ 10,11 ]…”

Gene Therapy for Liver Cancers: Current Status from Basic to Clinics

“…For example, it has been reported that the lipid nanoparticle-mediated delivery of Cas9 mRNA with AAVs encoding a sgRNA and a repair template to induce repair of a disease gene in adult animals showed successful genome editing and therapeutic effect [32]. Further efforts are necessary to develop the safe and effective delivery of the CRISPR/Cas9 system [180].…”

Niosome-Based Approach for In Situ Gene Delivery to Retina and Brain Cortex as Immune-Privileged Tissues

“…In addition to the previously described gene therapy approaches based on both gene supplementation and gene suppression strategies, recent advances on genome editing tools by CRISPR/Cas technology allow the correction of a specific mutation at a genomic level [18]. Due to the huge treatment possibilities of such revolutionary genome editing tools, the number of scientific publications in this area has considerably increased since 2014, and many clinical trials are underway, especially in cancer and pathological disorders of the blood and eye [19].…”