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SCIENCE CHINA Materials, Volume 60, Issue 6: 511-515(2017) https://doi.org/10.1007/s40843-016-5154-4

Tailoring non-viral delivery vehicles for transporting genome-editing tools

Wujin Sun1,2, Zhen Gu1,2,3,*
More info
  • ReceivedNov 8, 2016
  • AcceptedDec 13, 2016
  • PublishedDec 28, 2016

Abstract

The CRISPR-Cas system, especially the type II CRISPR-Cas9 system from Streptococcus pyogenes, has rapidly emerged as a popular genome editing tool. The development of Cas9 derivatives further expanded the toolbox of CRISPR-Cas9 based genome editing kit. However, therapeutic translation of the CRISPR-Cas9 system in vivo is severely impeded by the absence of an appropriate delivery carrier. The complexity and high molecular weight of the CRISPR-Cas9 system, together with the physiological barriers for nucleus targeted cargo transportation have made it a huge challenge for in vivo therapeutic CRISPR-Cas9 delivery. Currently, the main stream carriers for systemic delivery of CRISPR-Cas9 are viral based, such as adeno-associated virus. However, the safety concerns surrounding viral vectors call for the development of non-viral nanocarriers. In this review, we survey the recent advances in the development of non-viral delivery systems for CRISPR-Cas9. Challenges and future directions in this field are also discussed.


Funded by

the grants from NC TraCS

NIH’s Clinical and Translational Science Awards(CTSA,NIH grant 1UL1TR001111)

and Sloan Fellowship Award from the Alfred P. Sloan Foundation.


Acknowledgment

This work was supported by the grants from North Carolina TraCS, NIH’s Clinical and Translational Science Awards (CTSA, 1UL1TR001111) at UNC-CH, and Sloan Fellowship Award from the Alfred P. Sloan Foundation.


Interest statement

The authors declare that they have no conflict of interest.


Contributions statement

Sun W and Gu Z prepared the manuscript.


Author information

Wujin Sun received his BSs degree in bioengineering in 2010, followed by a MSc degree in biochemical engineering from Nanjing Tech University. He is currently a PhD student in Prof. Zhen Gu’s laboratory in the Joint Department of Biomedical Engineering at the University of North Carolina (UNC) at Chapel Hill and North Carolina University. His current research is focused on the development of non-viral delivery carriers for the CRISPR-Cas9 system.


Zhen Gu obtained his PhD degree at the University of California, Los Angeles (UCLA), under the guidance of Prof. Yi Tang at the Department of Chemical and Biomolecular Engineering. He was a postdoctoral associate working with Prof. Robert Langer at MIT and Harvard Medical School. He is currently an associate professor at the Joint Department of Biomedical Engineering at the UNC at Chapel Hill and North Carolina State University. He also holds a joint position in the UNC Eshelman School of Pharmacy and UNC Department of Medicine. His group studies controlled drug delivery, bioinspired materials and nanobiotechnology.


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  • Figure 1

    Recently developed nonviral systems for CRISPR-Cas9 delivery. (a) CPP mediated delivery of Cas9 protein and sgRNA, adapted with permission from [35]. (b) Cationic lipid for delivering Cas9/sgRNA ribonucleoprotein complex, adapted with permission from [32], Copyright 2014, Nature Publishing Group. (c) A DNA nanoclew based carrier was tailored via nucleic acid complementation for delivering the Cas9/sgRNA ribonucleoprotein, adapted with permission from [37], Copyright 2015, Wiley-VCH Verlag GmbH & Co. KGaA. (d) Lipid nanoparticle for delivery of Cas9 mRNA in combination with AAV delivered sgRNA and DNA donor, adapted with permission from [40], Copyright 2016, Nature Publishing Group.

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