RT Journal Article
SR Electronic
T1 CRISPR/Cas System for Genome Editing: Progress and Prospects as a Therapeutic Tool
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 725
OP 735
DO 10.1124/jpet.119.257287
VO 370
IS 3
A1 Sahel, Deepak Kumar
A1 Mittal, Anupama
A1 Chitkara, Deepak
YR 2019
UL http://jpet.aspetjournals.org/content/370/3/725.abstract
AB CRISPR was first observed in 1987 in bacteria and archaea and was later confirmed as part of bacterial adaptive immunity against the attacking phage. The CRISPR/Cas restriction system involves a restriction endonuclease enzyme guided by a hybrid strand of RNA consisting of CRISPR RNA and trans-activating RNA, which results in gene knockout or knockin followed by nonhomologous end joining and homology-directed repair. Owing to its efficiency, specificity, and reproducibility, the CRISPR/Cas restriction system was said to be a breakthrough in the field of biotechnology. Apart from its application in biotechnology, CRISPR/Cas has been explored for its therapeutic potential in several diseases including cancer, Alzheimer’s disease, sickle cell disease, Duchenne muscular dystrophy, neurologic disorders, etc., wherein CRISPR/Cas components such as Cas9/single guide RNA (sgRNA) ribonucleoprotein, sgRNA/mRNA, and plasmid were delivered. However, limitations including immunogenicity, low transfection, limited payload, instability, and off-target binding pose hurdles in its therapeutic use. Nonviral vectors (including cationic polymers, lipids, etc.), classically used as carriers for therapeutic genes, were used to deliver CRISPR/Cas components and showed interesting results. Herein, we discuss the CRISPR/Cas system and its brief history and classification, followed by its therapeutic applications using current nonviral delivery strategies.