ZFN-Mediated In Vivo Genome Editing Corrects Murine Hurler Syndrome.

Autor:	Ou L; Gene Therapy Center, University of Minnesota, Minneapolis, MN, USA., DeKelver RC; Sangamo Therapeutics, Inc., 501 Canal Boulevard, Richmond, CA, USA., Rohde M; Sangamo Therapeutics, Inc., 501 Canal Boulevard, Richmond, CA, USA., Tom S; Sangamo Therapeutics, Inc., 501 Canal Boulevard, Richmond, CA, USA., Radeke R; Sangamo Therapeutics, Inc., 501 Canal Boulevard, Richmond, CA, USA., St Martin SJ; Sangamo Therapeutics, Inc., 501 Canal Boulevard, Richmond, CA, USA., Santiago Y; Sangamo Therapeutics, Inc., 501 Canal Boulevard, Richmond, CA, USA., Sproul S; Sangamo Therapeutics, Inc., 501 Canal Boulevard, Richmond, CA, USA., Przybilla MJ; Center for Genome Engineering, Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN, USA., Koniar BL; Research Animal Resources, University of Minnesota, Minneapolis, MN, USA., Podetz-Pedersen KM; Center for Genome Engineering, Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN, USA., Laoharawee K; Center for Genome Engineering, Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN, USA., Cooksley RD; Gene Therapy Center, University of Minnesota, Minneapolis, MN, USA., Meyer KE; Sangamo Therapeutics, Inc., 501 Canal Boulevard, Richmond, CA, USA., Holmes MC; Sangamo Therapeutics, Inc., 501 Canal Boulevard, Richmond, CA, USA., McIvor RS; Center for Genome Engineering, Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN, USA., Wechsler T; Sangamo Therapeutics, Inc., 501 Canal Boulevard, Richmond, CA, USA., Whitley CB; Gene Therapy Center, University of Minnesota, Minneapolis, MN, USA. Electronic address: whitley@umn.edu.
Jazyk:	angličtina
Zdroj:	Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2019 Jan 02; Vol. 27 (1), pp. 178-187. Date of Electronic Publication: 2018 Nov 01.
DOI:	10.1016/j.ymthe.2018.10.018
Abstrakt:	Mucopolysaccharidosis type I (MPS I) is a severe disease due to deficiency of the lysosomal hydrolase α-L-iduronidase (IDUA) and the subsequent accumulation of the glycosaminoglycans (GAG), leading to progressive, systemic disease and a shortened lifespan. Current treatment options consist of hematopoietic stem cell transplantation, which carries significant mortality and morbidity risk, and enzyme replacement therapy, which requires lifelong infusions of replacement enzyme; neither provides adequate therapy, even in combination. A novel in vivo genome-editing approach is described in the murine model of Hurler syndrome. A corrective copy of the IDUA gene is inserted at the albumin locus in hepatocytes, leading to sustained enzyme expression, secretion from the liver into circulation, and subsequent uptake systemically at levels sufficient for correction of metabolic disease (GAG substrate accumulation) and prevention of neurobehavioral deficits in MPS I mice. This study serves as a proof-of-concept for this platform-based approach that should be broadly applicable to the treatment of a wide array of monogenic diseases. (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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