Delivering CRISPR: a review of the challenges and approaches

Lino, Christopher A.; Harper, Jason C.; Carney, James P.; Timlin, Jerilyn A.

doi:10.1080/10717544.2018.1474964

Title: Delivering CRISPR: a review of the challenges and approaches

Journal Article · Fri May 25 00:00:00 EDT 2018 · Drug Delivery

DOI:https://doi.org/10.1080/10717544.2018.1474964· OSTI ID:1483332

Lino, Christopher A. ^[1]; Harper, Jason C. ^[1]; Carney, James P. ^[1];

^[1]

Bioenergy and Defense Technologies, Sandia National Laboratories, Albuquerque, NM, USA

Gene therapy has long held promise to correct a variety of human diseases and defects. Discovery of the Clustered Regularly-Interspaced Short Palindromic Repeats (CRISPR), the mechanism of the CRISPR-based prokaryotic adaptive immune system (CRISPR-associated system, Cas), and its repurposing into a potent gene editing tool has revolutionized the field of molecular biology and generated excitement for new and improved gene therapies. Additionally, the simplicity and flexibility of the CRISPR/Cas9 site-specific nuclease system has led to its widespread use in many biological research areas including development of model cell lines, discovering mechanisms of disease, identifying disease targets, development of transgene animals and plants, and transcriptional modulation. In this review, we present the brief history and basic mechanisms of the CRISPR/Cas9 system and its predecessors (ZFNs and TALENs), lessons learned from past human gene therapy efforts, and recent modifications of CRISPR/Cas9 to provide functions beyond gene editing. We introduce several factors that influence CRISPR/Cas9 efficacy which must be addressed before effective in vivo human gene therapy can be realized. The focus then turns to the most difficult barrier to potential in vivo use of CRISPR/Cas9, delivery. We detail the various cargos and delivery vehicles reported for CRISPR/Cas9, including physical delivery methods (e.g. microinjection; electroporation), viral delivery methods (e.g. adeno-associated virus (AAV); full-sized adenovirus and lentivirus), and non-viral delivery methods (e.g. liposomes; polyplexes; gold particles), and discuss their relative merits. We also examine several technologies that, while not currently reported for CRISPR/Cas9 delivery, appear to have promise in this field. The therapeutic potential of CRISPR/Cas9 is vast and will only increase as the technology and its delivery improves.

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Research Organization:: Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

Sponsoring Organization:: USDOE National Nuclear Security Administration (NNSA); SNL Laboratory Directed Research and Development (LDRD) Program

Grant/Contract Number:: NA0003525

OSTI ID:: 1483332

Alternate ID(s):: OSTI ID: 1474089

Report Number(s):: SAND-2018-10248J; 112

Journal Information:: Drug Delivery, Journal Name: Drug Delivery Vol. 25 Journal Issue: 1; ISSN 1071-7544

Publisher:: Informa UK LimitedCopyright Statement

Country of Publication:: United Kingdom

Language:: English

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Cited by: 552 works

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Biomaterials as vectors for the delivery of CRISPR–Cas9 Eoh, Joon; Gu, Luo Biomaterials Science, Vol. 7, Issue 4 https://doi.org/10.1039/c8bm01310a	journal	January 2019
Designer Nucleases: Gene-Editing Therapies using CCR5 as an Emerging Target in HIV Almeida, Maria João; Matos, Ana Current HIV Research, Vol. 17, Issue 5 https://doi.org/10.2174/1570162x17666191025112918	journal	December 2019
CRISPR/Cas9 gene-editing strategies in cardiovascular cells Vermersch, Eva; Jouve, Charlène; Hulot, Jean-Sébastien Cardiovascular Research, Vol. 116, Issue 5 https://doi.org/10.1093/cvr/cvz250	journal	November 2019
CRISPR/Cas System for Genome Editing: Progress and Prospects as a Therapeutic Tool Sahel, Deepak Kumar; Mittal, Anupama; Chitkara, Deepak Journal of Pharmacology and Experimental Therapeutics, Vol. 370, Issue 3 https://doi.org/10.1124/jpet.119.257287	journal	May 2019
The Impact of HIV-1 Genetic Diversity on CRISPR-Cas9 Antiviral Activity and Viral Escape Darcis, Gilles; Binda, Caroline; Klaver, Bep Viruses, Vol. 11, Issue 3 https://doi.org/10.3390/v11030255	journal	March 2019
Enhanced gene transfection efficiency by low-dose 25 kDa polyethylenimine by the assistance of 1.8 kDa polyethylenimine Zhang, Hui; Chen, Zhiyi; Du, Meng Drug Delivery, Vol. 25, Issue 1 https://doi.org/10.1080/10717544.2018.1510065	journal	January 2018
3D-printing enabled micro-assembly of a microfluidic electroporation system for 3D tissue engineering Zhu, Qingfu; Hamilton, Megan; Vasquez, Bryan Lab on a Chip, Vol. 19, Issue 14 https://doi.org/10.1039/c9lc00046a	journal	January 2019
Targeted homology-directed repair in blood stem and progenitor cells with CRISPR nanoformulations Shahbazi, Reza; Sghia-Hughes, Gabriella; Reid, Jack L. Nature Materials, Vol. 18, Issue 10 https://doi.org/10.1038/s41563-019-0385-5	journal	May 2019
Synthetic Vehicles for Encapsulation and Delivery of CRISPR/Cas9 Gene Editing Machinery Carboni, Valentina; Maaliki, Carine; Alyami, Mram Advanced Therapeutics, Vol. 2, Issue 4 https://doi.org/10.1002/adtp.201800085	journal	February 2019
MS‐based strategies for identification of protein SUMOylation modification Sheng, Zenghua; Wang, Xixi; Ma, Yanni ELECTROPHORESIS, Vol. 40, Issue 21 https://doi.org/10.1002/elps.201900100	journal	June 2019
Viral Delivery Systems for CRISPR Xu, Christine L.; Ruan, Merry Z. C.; Mahajan, Vinit B. Viruses, Vol. 11, Issue 1 https://doi.org/10.3390/v11010028	journal	January 2019
A detached leaf assay for testing transient gene expression and gene editing in cowpea (Vigna unguiculata [L.] Walp.) Juranić, Martina; Nagahatenna, Dilrukshi S. K.; Salinas-Gamboa, Rigel Plant Methods, Vol. 16, Issue 1 https://doi.org/10.1186/s13007-020-00630-4	journal	June 2020

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