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J Control Release. 2017 Nov 28;266:17-26. doi: 10.1016/j.jconrel.2017.09.012. Epub 2017 Sep 11.

Delivery strategies of the CRISPR-Cas9 gene-editing system for therapeutic applications.

Author information

1
Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108, United States.
2
Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108, United States. Electronic address: chengkun@umkc.edu.

Abstract

The CRISPR-Cas9 genome-editing system is a part of the adaptive immune system in archaea and bacteria to defend against invasive nucleic acids from phages and plasmids. The single guide RNA (sgRNA) of the system recognizes its target sequence in the genome, and the Cas9 nuclease of the system acts as a pair of scissors to cleave the double strands of DNA. Since its discovery, CRISPR-Cas9 has become the most robust platform for genome engineering in eukaryotic cells. Recently, the CRISPR-Cas9 system has triggered enormous interest in therapeutic applications. CRISPR-Cas9 can be applied to correct disease-causing gene mutations or engineer T cells for cancer immunotherapy. The first clinical trial using the CRISPR-Cas9 technology was conducted in 2016. Despite the great promise of the CRISPR-Cas9 technology, several challenges remain to be tackled before its successful applications for human patients. The greatest challenge is the safe and efficient delivery of the CRISPR-Cas9 genome-editing system to target cells in human body. In this review, we will introduce the molecular mechanism and different strategies to edit genes using the CRISPR-Cas9 system. We will then highlight the current systems that have been developed to deliver CRISPR-Cas9 in vitro and in vivo for various therapeutic purposes.

KEYWORDS:

CRISPR-Cas9; Delivery; Gene therapy; Gene-editing; Nanoparticle; Non-viral delivery

PMID:
28911805
PMCID:
PMC5723556
DOI:
10.1016/j.jconrel.2017.09.012
[Indexed for MEDLINE]
Free PMC Article

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