Rational designs of in vivo CRISPR-Cas delivery systems

Cong-Fei Xu; Guo-Jun Chen; Ying-Li Luo; Yue Zhang; Gui Zhao; Zi-Dong Lu; Anna Czarna; Zhen Gu; Jun Wang

doi:10.1016/j.addr.2019.11.005

Rational designs of in vivo CRISPR-Cas delivery systems

Adv Drug Deliv Rev. 2021 Jan:168:3-29. doi: 10.1016/j.addr.2019.11.005. Epub 2019 Nov 21.

Authors

Cong-Fei Xu¹, Guo-Jun Chen², Ying-Li Luo³, Yue Zhang⁴, Gui Zhao⁵, Zi-Dong Lu³, Anna Czarna³, Zhen Gu⁶, Jun Wang⁷

Affiliations

¹ Guangzhou First People's Hospital, School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou 510006, PR China.
² Department of Bioengineering, California Nanosystems Institute, University of California, Los Angeles 90095, USA; Jonsson Comprehensive Cancer Center, California NanoSystems Institute, Center for Minimally Invasive Therapeutics, University of California, Los Angeles 90095, USA.
³ Institutes for Life Sciences, School of Medicine, South China University of Technology, Guangzhou 510006, PR China.
⁴ Guangzhou First People's Hospital, School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou 510006, PR China; Key Laboratory of Biomedical Engineering of Guangdong Province, and Innovation Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, PR China.
⁵ Guangzhou First People's Hospital, School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou 510006, PR China; Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou 510006, PR China.
⁶ Department of Bioengineering, California Nanosystems Institute, University of California, Los Angeles 90095, USA; Jonsson Comprehensive Cancer Center, California NanoSystems Institute, Center for Minimally Invasive Therapeutics, University of California, Los Angeles 90095, USA. Electronic address: guzhen@ucla.edu.
⁷ Guangzhou First People's Hospital, School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou 510006, PR China; National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, PR China; Key Laboratory of Biomedical Engineering of Guangdong Province, and Innovation Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, PR China; Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510005, PR China. Electronic address: mcjwang@scut.edu.cn.

PMID: 31759123
DOI: 10.1016/j.addr.2019.11.005

Abstract

The CRISPR-Cas system initiated a revolution in genome editing when it was, for the first time, demonstrated success in the mammalian cells. Today, scientists are able to readily edit genomes, regulate gene transcription, engineer posttranscriptional events, and image nucleic acids using CRISPR-Cas-based tools. However, to efficiently transport CRISPR-Cas into target tissues/cells remains challenging due to many extra- and intra-cellular barriers, therefore largely limiting the applications of CRISPR-based therapeutics in vivo. In this review, we summarize the features of plasmid-, RNA- and ribonucleoprotein (RNP)-based CRISPR-Cas therapeutics. Then, we survey the current in vivo delivery systems. We specify the requirements for efficient in vivo delivery in clinical settings, and highlight both efficiency and safety for different CRISPR-Cas tools.

Keywords: CRISPR-Cas; Drug delivery; Genome editing; Nanomedicine.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

CRISPR-Cas Systems / genetics*
Clustered Regularly Interspaced Short Palindromic Repeats / genetics*
Drug Delivery Systems
Epigenome / genetics
Exosomes / metabolism
Gene Editing / methods*
Gene Regulatory Networks / physiology
Genetic Vectors / metabolism
Lipids / chemistry
Nanoparticles / chemistry
RNA / metabolism
Transcription, Genetic / physiology

Substances

Lipids
RNA