PT  - JOURNAL ARTICLE
AU  - Sahel, Deepak Kumar
AU  - Mittal, Anupama
AU  - Chitkara, Deepak
TI  - CRISPR/Cas System for Genome Editing: Progress and Prospects as a Therapeutic Tool
AID  - 10.1124/jpet.119.257287
DP  - 2019 Sep 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 725--735
VI  - 370
IP  - 3
4099  - http://jpet.aspetjournals.org/content/370/3/725.short
4100  - http://jpet.aspetjournals.org/content/370/3/725.full
SO  - J Pharmacol Exp Ther2019 Sep 01; 370
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.