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The delivery challenge: fulfilling the promise of therapeutic genome editing.
Nat Biotechnol. 2020 Jul; 38(7):845-855.NBio

Abstract

Genome editing has the potential to treat an extensive range of incurable monogenic and complex diseases. In particular, advances in sequence-specific nuclease technologies have dramatically accelerated the development of therapeutic genome editing strategies that are based on either the knockout of disease-causing genes or the repair of endogenous mutated genes. These technologies are progressing into human clinical trials. However, challenges remain before the therapeutic potential of genome editing can be fully realized. Delivery technologies that have serendipitously been developed over the past couple decades in the protein and nucleic acid delivery fields have been crucial to genome editing success to date, including adeno-associated viral and lentiviral vectors for gene therapy and lipid nanoparticle and other non-viral vectors for nucleic acid and protein delivery. However, the efficiency and tissue targeting capabilities of these vehicles must be further improved. In addition, the genome editing enzymes themselves need to be optimized, and challenges regarding their editing efficiency, specificity and immunogenicity must be addressed. Emerging protein engineering and synthetic chemistry approaches can offer solutions and enable the development of safe and efficacious clinical genome editing.

Authors+Show Affiliations

California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, CA, USA.Department of Bioengineering, University of California, Berkeley, CA, USA. Innovative Genomics Institute (IGI), University of California, Berkeley, CA, USA.Department of Bioengineering, University of California, Berkeley, CA, USA.California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, CA, USA. nmurthy@berkeley.edu. Department of Bioengineering, University of California, Berkeley, CA, USA. nmurthy@berkeley.edu. Innovative Genomics Institute (IGI), University of California, Berkeley, CA, USA. nmurthy@berkeley.edu.California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, CA, USA. schaffer@berkeley.edu. Department of Bioengineering, University of California, Berkeley, CA, USA. schaffer@berkeley.edu. Innovative Genomics Institute (IGI), University of California, Berkeley, CA, USA. schaffer@berkeley.edu. Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA, USA. schaffer@berkeley.edu. Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA. schaffer@berkeley.edu. Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA. schaffer@berkeley.edu.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

32601435

Citation

van Haasteren, Joost, et al. "The Delivery Challenge: Fulfilling the Promise of Therapeutic Genome Editing." Nature Biotechnology, vol. 38, no. 7, 2020, pp. 845-855.
van Haasteren J, Li J, Scheideler OJ, et al. The delivery challenge: fulfilling the promise of therapeutic genome editing. Nat Biotechnol. 2020;38(7):845-855.
van Haasteren, J., Li, J., Scheideler, O. J., Murthy, N., & Schaffer, D. V. (2020). The delivery challenge: fulfilling the promise of therapeutic genome editing. Nature Biotechnology, 38(7), 845-855. https://doi.org/10.1038/s41587-020-0565-5
van Haasteren J, et al. The Delivery Challenge: Fulfilling the Promise of Therapeutic Genome Editing. Nat Biotechnol. 2020;38(7):845-855. PubMed PMID: 32601435.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The delivery challenge: fulfilling the promise of therapeutic genome editing. AU - van Haasteren,Joost, AU - Li,Jie, AU - Scheideler,Olivia J, AU - Murthy,Niren, AU - Schaffer,David V, Y1 - 2020/06/29/ PY - 2018/11/02/received PY - 2020/05/19/accepted PY - 2020/7/1/pubmed PY - 2020/7/1/medline PY - 2020/7/1/entrez SP - 845 EP - 855 JF - Nature biotechnology JO - Nat. Biotechnol. VL - 38 IS - 7 N2 - Genome editing has the potential to treat an extensive range of incurable monogenic and complex diseases. In particular, advances in sequence-specific nuclease technologies have dramatically accelerated the development of therapeutic genome editing strategies that are based on either the knockout of disease-causing genes or the repair of endogenous mutated genes. These technologies are progressing into human clinical trials. However, challenges remain before the therapeutic potential of genome editing can be fully realized. Delivery technologies that have serendipitously been developed over the past couple decades in the protein and nucleic acid delivery fields have been crucial to genome editing success to date, including adeno-associated viral and lentiviral vectors for gene therapy and lipid nanoparticle and other non-viral vectors for nucleic acid and protein delivery. However, the efficiency and tissue targeting capabilities of these vehicles must be further improved. In addition, the genome editing enzymes themselves need to be optimized, and challenges regarding their editing efficiency, specificity and immunogenicity must be addressed. Emerging protein engineering and synthetic chemistry approaches can offer solutions and enable the development of safe and efficacious clinical genome editing. SN - 1546-1696 UR - https://www.unboundmedicine.com/medline/citation/32601435/The_delivery_challenge:_fulfilling_the_promise_of_therapeutic_genome_editing L2 - https://dx.doi.org/10.1038/s41587-020-0565-5 DB - PRIME DP - Unbound Medicine ER -
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