Abstract:
Gene editing technologies refer to a type of gene engineering to inactivate genes, correct mutated sequences, or insert intact genes. Great progresses in the gene editing tools, including clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9), have been made in recent years. A short single guide RNA (sgRNA) with the sequences that can bind to a specific target sequence of DNA and also bind to the Cas9 enzyme has been used to guide Cas9 to cut the DNA at the targeted location and induce the breakage of double-strand DNA, showing great potentials for the treatment of many diseases. Efficient delivery of CRISPR/Cas9 into the cells is the key to improve the gene editing efficiency. Viral CRISPR/Cas9 delivery systems have been widely used in the studies and clinical translation of CRISPR/Cas9-based gene editing. Although all viral vector genomes have been modified by removing some areas in the genomes so that the replication becomes deranged and thereby makes the virus be safer, some critical problems still exist, such as the immunogenicity that may cause inflammatory, toxin production, and the limitation in transgenic capacity size. Relative to viral delivery systems, nonviral delivery systems possess significant advantages in biosafety and large-scale production, which have attracted great attention for the delivery of CRISPR/Cas9. Indeed, great progresses in nonviral CRISPR/Cas9 delivery systems have been made in recent years. Various efficient biodegradable and biocompatible systems have been developed for
in vitro and
in vivo applications. In this review, the advantages of nonviral delivery systems compared to the typical viral delivery systems were discussed, and then the recent progresses in lipid and polymer delivery systems were primarily summarized. Among them, the representative examples were discussed in detail. Finally, the conclusions and perspectives concerning the obstacles of nonviral CRISPR/Cas9 delivery systems as well as further development direction were proposed.