ZFN-Mediated In Vivo Genome Editing Corrects Murine Hurler Syndrome

Li Ou; Russell C. DeKelver; Michelle Rohde; Susan Tom; Robert Radeke; Susan J. St. Martin; Yolanda Santiago; Scott Sproul; Michelle J. Przybilla; Brenda L. Koniar; Kelly M. Podetz-Pedersen; Kanut Laoharawee; Renee D. Cooksley; Kathleen E. Meyer; Michael C. Holmes; R. Scott McIvor; Thomas Wechsler; Chester B. Whitley

doi:10.1016/j.ymthe.2018.10.018

ZFN-Mediated In Vivo Genome Editing Corrects Murine Hurler Syndrome

Li Ou, Russell C. DeKelver, Michelle Rohde, Susan Tom, Robert Radeke, Susan J. St. Martin, Yolanda Santiago, Scott Sproul, Michelle J. Przybilla, Brenda L. Koniar, Kelly M. Podetz-Pedersen, Kanut Laoharawee, Renee D. Cooksley, Kathleen E. Meyer, Michael C. Holmes, R. Scott McIvor, Thomas Wechsler, Chester B. Whitley

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Abstract

In vivo genome editing following a single injection of ZFN and IDUA donor encoding AAV8 resulted in metabolic correction and neurological benefit in a murine model of MPS I. These results enable a currently open clinical trial to evaluate targeted genome engineering for MPS I in humans.

Original language	English (US)
Pages (from-to)	178-187
Number of pages	10
Journal	Molecular Therapy
Volume	27
Issue number	1
DOIs	https://doi.org/10.1016/j.ymthe.2018.10.018
State	Published - Jan 2 2019

Bibliographical note

Funding Information:
The authors would like to thank Carolyn Gaspar, Anne-Marie Ledeboer, Melanie Butler, and Amy Manning-Bog for assistance in necropsy and figure preparation, Seventh Wave Laboratories (Maryland Heights, MO) for performing necropsy and histopathology evaluation (Mark Martinez, DVM, DACVP), and Pacific BioLabs (Hercules, CA) for performing mass-spectrometry analysis of dermatan and heparan sulfate levels (Rick Staub and Vy Tran). This work was supported by Sangamo Therapeutics .

Funding Information:
The authors would like to thank Carolyn Gaspar, Anne-Marie Ledeboer, Melanie Butler, and Amy Manning-Bog for assistance in necropsy and figure preparation, Seventh Wave Laboratories (Maryland Heights, MO) for performing necropsy and histopathology evaluation (Mark Martinez, DVM, DACVP), and Pacific BioLabs (Hercules, CA) for performing mass-spectrometry analysis of dermatan and heparan sulfate levels (Rick Staub and Vy Tran). This work was supported by Sangamo Therapeutics.

Publisher Copyright:
© 2018 The Author(s)

Keywords

gene editing
gene therapy
lysosomal diseases

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10.1016/j.ymthe.2018.10.018

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319315

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Ou, L., DeKelver, R. C., Rohde, M., Tom, S., Radeke, R., St. Martin, S. J., Santiago, Y., Sproul, S., Przybilla, M. J., Koniar, B. L., Podetz-Pedersen, K. M., Laoharawee, K., Cooksley, R. D., Meyer, K. E., Holmes, M. C., McIvor, R. S., Wechsler, T., & Whitley, C. B. (2019). ZFN-Mediated In Vivo Genome Editing Corrects Murine Hurler Syndrome. Molecular Therapy, 27(1), 178-187. https://doi.org/10.1016/j.ymthe.2018.10.018

Ou, L, DeKelver, RC, Rohde, M, Tom, S, Radeke, R, St. Martin, SJ, Santiago, Y, Sproul, S, Przybilla, MJ , Koniar, BL, Podetz-Pedersen, KM, Laoharawee, K, Cooksley, RD, Meyer, KE, Holmes, MC, McIvor, RS, Wechsler, T & Whitley, CB 2019, 'ZFN-Mediated In Vivo Genome Editing Corrects Murine Hurler Syndrome', Molecular Therapy, vol. 27, no. 1, pp. 178-187. https://doi.org/10.1016/j.ymthe.2018.10.018

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ZFN-Mediated In Vivo Genome Editing Corrects Murine Hurler Syndrome

Abstract

Bibliographical note

Keywords

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