176
Views
0
CrossRef citations to date
0
Altmetric
Review

Ex vivo gene therapy for lysosomal storage disorders: future perspectives

ORCID Icon, , ORCID Icon, , , ORCID Icon & ORCID Icon show all
Pages 353-364 | Received 14 Nov 2022, Accepted 14 Mar 2023, Published online: 20 Mar 2023

References

  • Platt FM, d’Azzo A, Davidson BL, et al. Lysosomal Storage diseases. Nat Rev Dis Primers. 2018;4(1):27. DOI:10.1038/s41572-018-0025-4
  • Platt FM, Boland B, van der Spoel AC. The cell biology of disease: lysosomal storage disorders: the cellular impact of lysosomal dysfunction. J Cell Biol. 2012;199(5):723–734.
  • Poswar FO, Vairo F, Burin M, et al. Lysosomal diseases: overview on current diagnosis and treatment. Genet Mol Biol. 2019;42(1 suppl 1):165–177. DOI:10.1590/1678-4685-gmb-2018-0159
  • Solomon M, Muro S. Lysosomal enzyme replacement therapies: historical development, clinical outcomes, and future perspectives. Adv Drug Deliv Rev. 2017;118:109–134.
  • Scotto Rosato A, Krogsaeter EK, Jaślan D, et al. TPC2 rescues lysosomal storage in mucolipidosis type IV , Niemann–Pick type C1, and Batten disease. EMBO Mol Med. 2022;14(9):e15377. DOI:10.15252/emmm.202115377
  • Matte U, Pasqualim G. Lysosome: the Story Beyond the Storage. J Inherit Metab Dis. 2016;4. DOI:10.1177/2326409816679431
  • Sun A. Lysosomal storage disease overview. Ann Transl Med. 2018;6(24):476.
  • Vera LNP, Schuh RS, Fachel FNS, et al. Brain and visceral gene editing of mucopolysaccharidosis I mice by nasal delivery of the CRISPR/Cas9 system. J Gene Med. 2022;24(4):e3410. DOI:10.1002/jgm.3410
  • Pardridge WM. Blood-brain barrier delivery for lysosomal storage disorders with IgG-lysosomal enzyme fusion proteins. Adv Drug Deliv Rev. 2022;184:114234.
  • Journal of Gene Medicine Database on Gene Therapy Clinical Trials Worldwide. Last accessed Oct 2 2022.
  • Crystal RG. Adenovirus: the first effective in vivo gene delivery vector. Hum Gene Ther. 2014;25(1):3–11.
  • Maetzig T, Galla M, Baum C, et al. Gammaretroviral vectors: biology, technology and application. Viruses. 2011;3:677–713.
  • Naldini L, Blömer U, Gallay P, et al. In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science. 1996;272:263–267.
  • Alok VJ, Salemiz S. Pseudotyped Lentiviral Vectors: one Vector, Many Guises. Hum Gene Ther Methods. 2017;28(6):291–301.
  • Wang D, Tai PWL, Gao G. Adeno-associated virus vector as a platform for gene therapy delivery. Nat Rev Drug Discov. 2019;18(5):358–378.
  • Wu Z, Asokan A, Samulski RJ. Adeno-associated virus serotypes: vector toolkit for human gene therapy. Mol Ther. 2006;14(3):316–327.
  • Chandrasegaran S, Carroll D. Origins of Programmable Nucleases for Genome Engineering. J Mol Biol. 2016;428:963–989.
  • Xue C, Greene EC. DNA Repair Pathway Choices in CRISPR-Cas9-Mediated Genome Editing. Trends in genetics: tIG. Trends Genet. 2021;37(7):639–656.
  • Urnov FD, Rebar EJ, Holmes MC, et al. Genome editing with engineered zinc finger nucleases. Nat Rev Genet. 2010;11:636–646.
  • Christian M, Cermak T, Doyle EL, et al. Targeting DNA double-strand breaks with TAL effector nucleases. Genetics. 2010;186:757–761.
  • Mussolino C, Alzubi J, Fine EJ, et al. Talens facilitate targeted genome editing in human cells with high specificity and low cytotoxicity. Nucleic Acids Res. 2014;42:6762–6773.
  • Jinek M, Chylinski K, Fonfara I, et al. A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity. Science. 2012;337(6096):816–821. DOI:10.1126/science.1225829
  • Nahmad AD, Reuveni E, Goldschmidt E, et al. Frequent aneuploidy in primary human T cells after CRISPR–Cas9 cleavage. Nature Biotechnol. 40(12). Online ahead of print. 1807–1813. 2022 Jun 30. 10.1038/s41587-022-01377-0.
  • Kim HK, Lee S, Kim Y, et al. High-throughput analysis of the activities of xCas9, SpCas9-NG and SpCas9 at matched and mismatched target sequences in human cells. Nat Biomed Eng. 2020;4:111–124.
  • Edraki A, Mir A, Ibraheim R, et al. A Compact, High-Accuracy Cas9 with a Dinucleotide PAM for in vivo Genome Editing. Genome Editing Molecular Cell. 2019;73(4):714–726 e4. DOI:10.1016/j.molcel.2018.12.003
  • Kleinstiver BP, Tsai SQ, Prew MS, et al. Genome-wide specificities of CRISPR-Cas Cpf1 nucleases in human cells. Nature Biotechnol. 2016;34:869–874.
  • Zhang W, Yin J, Zhang-Ding Z, et al. In-depth assessment of the PAM compatibility and editing activities of Cas9 variants. Nucleic Acids Res. 2021;49:8785–8795.
  • Vakulskas CA, Dever DP, Rettig GR, et al. A high-fidelity Cas9 mutant delivered as a ribonucleoprotein complex enables efficient gene editing in human hematopoietic stem and progenitor cells. Nature Med. 2018;24:1216–1224.
  • Samuelson C, Radtke S, Zhu H, et al. Multiplex CRISPR/Cas9 genome editing in hematopoietic stem cells for fetal hemoglobin reinduction generates chromosomal translocations. Mol Ther - Methods Clin Dev. 2021;23:507–523.
  • Amendola M, Brusson M, Miccio A. Crisprthripsis: the Risk of CRISPR/Cas9-induced Chromothripsis in Gene Therapy. Stem Cells Transl Med. 2022;11:1003–1009.
  • Enache OM, Rendo V, Abdusamad M, et al. Cas9 activates the p53 pathway and selects for p53-inactivating mutations. Nature Genet. 2020;52:662–668.
  • Komor AC, Kim YB, Packer MS, et al. Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature. 2016;533:420–424.
  • Anzalone AV, Randolph PB, Davis JR, et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature. 2019;576:149–157.
  • Jiang T, Zhang XO, Weng Z, et al. Deletion and replacement of long genomic sequences using prime editing. Nature Biotechnol. 2022;40(2):227–234. DOI:10.1038/s41587-021-01026-y
  • Yarnall MTN, Ioannidi EI, Schmitt-Ulms C, et al. Drag-and-drop genome insertion of large sequences without double-strand DNA cleavage using CRISPR-directed integrases. Nature Biotechnol. 2022. Online ahead of print. 10.1038/s41587-022-01527-4
  • Boucher AA, Miller W, Shanley R, et al. Long-term outcomes after allogeneic hematopoietic stem cell transplantation for metachromatic leukodystrophy: the largest single-institution cohort report. Orphanet J Rare Dis. 2015;10(1):94. DOI:10.1186/s13023-015-0313-y
  • Biffi A, Capotondo A, Fasano S, et al. Gene therapy of metachromatic leukodystrophy reverses neurological damage and deficits in mice. J Clin Invest. 2006;116(11):3070–3082. DOI:10.1172/JCI28873
  • Sessa M, Lorioli L, Fumagalli F, et al. Lentiviral haemopoietic stem-cell gene therapy in early-onset metachromatic leukodystrophy: an ad-hoc analysis of a non-randomised, open-label, phase 1/2 trial. Lancet. 2016;388(10043):476–487. DOI:10.1016/S0140-6736(16)30374-9
  • Biffi A, Montini E, Lorioli L, et al. Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy. Science. 2013;341:1233158.
  • Fumagalli F, Calbi V, Natali Sora MG, et al. Lentiviral haematopoietic stem-cell gene therapy for early-onset metachromatic leukodystrophy: long-term results from a non-randomised, open-label, phase 1/2 trial and expanded access. Lancet. 2022;399(10322):372–383. DOI:10.1016/S0140-6736(21)02017-1.
  • Meneghini V, Frati G, Sala D, et al. Generation of Human Induced Pluripotent Stem Cell-Derived Bona Fide Neural Stem Cells for Ex vivo Gene Therapy of Metachromatic Leukodystrophy. Stem Cells Transl Med. 2017;6(2):352–368. DOI:10.5966/sctm.2015-0414
  • Doerr J, Bockenhoff A, Ewald B, et al. Arylsulfatase a Overexpressing Human iPSC-derived Neural Cells Reduce CNS Sulfatide Storage in a Mouse Model of Metachromatic Leukodystrophy. Mol Ther. 2015;23(9):1519–1531. DOI:10.1038/mt.2015.106
  • Allewelt H, Taskindoust M, Troy J. Long-Term Functional Outcomes after Hematopoietic Stem Cell Transplant for Early Infantile Krabbe Disease. Biol Blood Marrow Transplant. 2018;24(11):2233–2238.
  • Visigalli I, Ungari S, Martino S, et al. The galactocerebrosidase enzyme contributes to the maintenance of a functional hematopoietic stem cell niche. Blood. 2010;116:1857–1866.
  • Gentner B, Visigalli I, Hiramatsu H, et al. Identification of Hematopoietic Stem Cell–Specific miRnas Enables Gene Therapy of Globoid Cell Leukodystrophy. Sci Transl Med. 2010;2(58):58ra84. DOI:10.1126/scitranslmed.3001522
  • Ungari S, Montepeloso A, Morena F, et al. Design of a regulated lentiviral vector for hematopoietic stem cell gene therapy of globoid cell leukodystrophy. Mol Ther Methods Clin Dev. 2015;2:15038.
  • Hu P, Li Y, Nikolaishvili-Feinberg N, et al. Hematopoietic Stem cell transplantation and lentiviral vector-based gene therapy for Krabbe’s disease: present convictions and future prospects. J Neurosci Res. 2016;94(11):1152–1168. DOI:10.1002/jnr.23847
  • Stirnemann J, Belmatoug N, Camou F, et al. A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments. Int J Mol Sci. 2017;18(2):441. DOI:10.3390/ijms18020441
  • Donald A, Bjorkvall CK, Vellodi A, et al. Thirty-year clinical outcomes after haematopoietic stem cell transplantation in neuronopathic Gaucher disease. Orphanet J Rare Dis. 2022;17(1):234. DOI:10.1186/s13023-022-02378-7
  • Dunbar CE, Kohn DB, Schiffmann R, et al. Retroviral transfer of the glucocerebrosidase gene into CD34+ cells from patients with Gaucher disease: in vivo detection of transduced cells without myeloablation. Hum Gene Ther. 1998;9:2629–2640.
  • Kim EY, Hong YB, Lai Z, et al. Long-term expression of the human glucocerebrosidase gene in vivo after transplantation of bone-marrow-derived cells transformed with a lentivirus vector. J Gene Med. 2005;7(7):878–887. DOI:10.1002/jgm.732
  • Enquist IB, Nilsson E, Ooka A, et al. Effective cell and gene therapy in a murine model of Gaucher disease. Proc Natl Acad Sci U S A. 2006;103(37):13819–13824. DOI:10.1073/pnas.0606016103
  • Enquist IB, Nilsson E, Mansson JE, et al. Successful low-risk hematopoietic cell therapy in a mouse model of type 1 Gaucher disease. Stem Cells. 2009;27(3):744–752. DOI:10.1634/stemcells.2008-0844
  • Dahl M, Smith EMK, Warsi S, et al. Correction of pathology in mice displaying Gaucher disease type 1 by a clinically-applicable lentiviral vector. Mol Ther Methods Clin Dev. 2021;20:312–323.
  • Scharenberg SG, Poletto E, Lucot KL, et al. Engineering monocyte/macrophage-specific glucocerebrosidase expression in human hematopoietic stem cells using genome editing. Nat Commun. 2020;11(1):3327. DOI:10.1038/s41467-020-17148-x.
  • Takenaka T, Qin G, Brady RO, et al. Circulating alpha-galactosidase a derived from transduced bone marrow cells: relevance for corrective gene transfer for Fabry disease. Hum Gene Ther. 1999;10(12):1931–1939. DOI:10.1089/10430349950017293
  • Takenaka T, Hendrickson CS, Tworek DM, et al. Enzymatic and functional correction along with long-term enzyme secretion from transduced bone marrow hematopoietic stem/progenitor and stromal cells derived from patients with Fabry disease. Exp Hematol. 1999;27(7):1149–1159. DOI:10.1016/S0301-472X(99)00050-8
  • Yoshimitsu M, Higuchi K, Ramsubir S, et al. Efficient correction of Fabry mice and patient cells mediated by lentiviral transduction of hematopoietic stem/progenitor cells. Gene Ther. 2007;14(3):256–265. DOI:10.1038/sj.gt.3302839
  • Ohshima T, Murray GJ, Swaim WD, et al. α-Galactosidase a deficient mice: a model of Fabry disease. Proc Natl Acad Sci U S A. 1997;94(6):2540–2544. DOI:10.1073/pnas.94.6.2540
  • Pacienza N, Yoshimitsu M, Mizue N, et al. Lentivector transduction improves outcomes over transplantation of human HSCs alone in NOD/SCID/Fabry mice. Mol Ther. 2012;20(7):1454–1461. DOI:10.1038/mt.2012.64
  • Khan A, Barber DL, Huang J, et al. Lentivirus-mediated gene therapy for Fabry disease. Nat Commun. 2021;12(1):1178. DOI:10.1038/s41467-021-21371-5
  • Kami D, Suzuki Y, Yamanami M, et al. Genetically Modified Cell Transplantation Through Macroencapsulated Spheroids with Scaffolds to Treat Fabry Disease. Cell Transplant. 2021;30:9636897211060269.
  • Nagree MS, Felizardo TC, Faber ML, et al. Autologous, lentivirus-modified, T-rapa cell “micropharmacies” for lysosomal storage disorders. EMBO Mol Med. 2022;14(4):e14297. DOI:10.15252/emmm.202114297
  • Ramsubir S, Nonaka T, Girbes CB, et al. In vivo delivery of human acid ceramidase via cord blood transplantation and direct injection of lentivirus as novel treatment approaches for Farber disease. Mol Genet Metab. 2008;95(3):133–141. DOI:10.1016/j.ymgme.2008.08.003
  • Walia JS, Neschadim A, Lopez-Perez O, et al. Autologous Transplantation of Lentivector/Acid Ceramidase–Transduced Hematopoietic Cells in Nonhuman Primates. Hum Gene Ther. 2011;22(6):679–687. DOI:10.1089/hum.2010.195
  • Schuchman EH, Desnick RJ. Types a and B Niemann-Pick disease. Mol Genet Metab. 2017;120(1–2):27–33.
  • Jin HK, Schuchman EH. Ex vivo gene therapy using bone marrow-derived cells: combined effects of intracerebral and intravenous transplantation in a mouse model of niemann–pick disease. Mol Ther. 2003;8(6):876–885.
  • Sano R, Tessitore A, Ingrassia A, et al. Chemokine-induced recruitment of genetically modified bone marrow cells into the CNS of GM1-gangliosidosis mice corrects neuronal pathology. Blood. 2005;106:2259–2268.
  • Tsunogai T, Ohashi T, Shimada Y, et al. Hematopoietic stem cell gene therapy ameliorates CNS involvement in murine model of GM1-gangliosidosis. Mol Ther Methods Clin Dev. 2022;25:448–460.
  • Syres K, Harrison F, Tadlock M, et al. Successful treatment of the murine model of cystinosis using bone marrow cell transplantation. Blood. 2009;114:2542–2552.
  • Harrison F, Yeagy BA, Rocca CJ, et al. Hematopoietic stem cell gene therapy for the multisystemic lysosomal storage disorder cystinosis. Mol Ther. 2013;21(2):433–444. DOI:10.1038/mt.2012.214
  • Naphade S, Sharma J, Gaide Chevronnay HP, et al. Brief reports: lysosomal cross-correction by hematopoietic stem cell-derived macrophages via tunneling nanotubes. Stem Cells. 2015;33:301–309.
  • Kohler L, Puertollano R, Raben N. Pompe Disease: from Basic Science to Therapy. Neurotherapeutics. 2018;15:928–942.
  • Douillard-Guilloux G, Richard E, Batista L, et al. Partial phenotypic correction and immune tolerance induction to enzyme replacement therapy after hematopoietic stem cell gene transfer of α-glucosidase in Pompe disease. J Gene Med. 2009;11(4):279–287. DOI:10.1002/jgm.1305
  • van Til Np, Stok M, Aerts Kaya FSF, et al. Lentiviral gene therapy of murine hematopoietic stem cells ameliorates the Pompe disease phenotype. Blood. 2010;115(26):5329–5337. DOI:10.1182/blood-2009-11-252874
  • Stok M, de Boer H, Huston MW, et al. Lentiviral Hematopoietic Stem Cell Gene Therapy Corrects Murine Pompe Disease. Mol Ther Methods Clin Dev. 2020;17:1014–1025.
  • Piras G, Montiel-Equihua C, Chan YA, et al. Lentiviral Hematopoietic Stem Cell Gene Therapy Rescues Clinical Phenotypes in a Murine Model of Pompe Disease. Mol Ther Methods Clin Dev. 2020;18:558–570.
  • Liang Q, Vlaar EC, Catalano F, et al. Lentiviral gene therapy prevents anti-human acid alpha-glucosidase antibody formation in murine Pompe disease. Mol Ther Methods Clin Dev. 2022;25:520–532.
  • D’avanzo F, Rigon L, Zanetti A, et al. Mucopolysaccharidosis Type II: one Hundred Years of Research, Diagnosis, and Treatment. Int J Mol Sci. 2020;21(4):1258.
  • Kubaski F, Yabe H, Suzuki Y, et al. Hematopoietic Stem Cell Transplantation for Patients with Mucopolysaccharidosis II. Biol Blood Marrow Transplant. 2017;23:1795–1803.
  • Sonoda H, Morimoto H, Yoden E, et al. A Blood-Brain-Barrier-Penetrating Anti-human Transferrin Receptor Antibody Fusion Protein for Neuronopathic Mucopolysaccharidosis II. Mol Ther. 2018;26:1366–1374.
  • Muenzer J, Hendriksz CJ, Fan Z, et al. A phase I/II study of intrathecal idursulfase-IT in children with severe mucopolysaccharidosis II. Genet Med. 2016;18:73–81.
  • High KA, Roncarolo MG. Gene Therapy. N Engl J Med. 2019;381:455–464.
  • Shull RM, Lu X, McEntee MF, et al. Myoblast Gene Therapy in Canine Mucopolysaccharidosis I: abrogation by an Immune Response to α - l -Iduronidase. Hum Gene Ther. 1996;7(13):1595–1603. DOI:10.1089/hum.1996.7.13-1595
  • Ohashi T, Yokoo T, Iizuka S, et al. Reduction of lysosomal storage in murine mucopolysaccharidosis type VII by transplantation of normal and genetically modified macrophages. Blood. 2000;95:3631–3633.
  • Sakurai K, Iizuka S, Shen JS, et al. Brain transplantation of genetically modified bone marrow stromal cells corrects CNS pathology and cognitive function in MPS VII mice. Genet Ther. 2004;11(19):1475–1481. DOI:10.1038/sj.gt.3302338
  • Meyerrose TE, Roberts M, Ohlemiller KK, et al. Lentiviral-transduced human mesenchymal stem cells persistently express therapeutic levels of enzyme in a xenotransplantation model of human disease. Stem Cells. 2008;26:1713–1722.
  • Walton RM, Magnitsky SG, Seiler GS, et al. Transplantation and magnetic resonance imaging of canine neural progenitor cell grafts in the postnatal dog brain. J Neuropathol Exp Neurol. 2008;67:954–962.
  • Miki T, Vazquez L, Yanuaria L, et al. Induced Pluripotent Stem Cell Derivation and Ex vivo Gene Correction Using a Mucopolysaccharidosis Type 1 Disease Mouse Model. Stem Cells Int. 2019;2019:6978303.
  • Griffin TA, Anderson HC, Wolfe JH. Ex vivo gene therapy using patient iPSC-derived NSCs reverses pathology in the brain of a homologous mouse model. Stem Cell Rep. 2015;4:835–846.
  • Gentner B, Tucci F, Galimberti S, et al. Hematopoietic Stem- and Progenitor-Cell Gene Therapy for Hurler Syndrome. N Engl J Med. 2021;385:1929–1940.
  • Fraldi A, Hemsley K, Crawley A, et al. Functional correction of CNS lesions in an MPS-IIIA mouse model by intracerebral AAV-mediated delivery of sulfamidase and SUMF1 genes. Hum Mol Genet. 2007;16:2693–2702.
  • Langford-Smith A, Wilkinson FL, Langford-Smith KJ, et al. Hematopoietic stem cell and gene therapy corrects primary neuropathology and behavior in mucopolysaccharidosis IIIA mice. Mol Ther. 2012;20:1610–1621.
  • Ruzo A, Marco S, Garcia M, et al. Correction of pathological accumulation of glycosaminoglycans in central nervous system and peripheral tissues of MPSIIIA mice through systemic AAV9 gene transfer. Hum Gene Ther. 2012;23(12):1237–1246. DOI:10.1089/hum.2012.029
  • Sergijenko A, Langford-Smith A, Liao AY, et al. Myeloid/Microglial driven autologous hematopoietic stem cell gene therapy corrects a neuronopathic lysosomal disease. Mol Ther. 2013;21:1938–1949.
  • Ellison SM, Liao A, Wood S, et al. Pre-clinical Safety and Efficacy of Lentiviral Vector-Mediated Ex vivo Stem Cell Gene Therapy for the Treatment of Mucopolysaccharidosis IIIA. Mol Ther - Methods Clin Dev. 2019;13:399–413.
  • Parker H, Ellison SM, Holley RJ, et al. Haematopoietic stem cell gene therapy with IL-1Ra rescues cognitive loss in mucopolysaccharidosis IIIA. EMBO Mol Med. 2020;12:e11185.
  • Holley RJ, Ellison SM, Fil D, et al. Macrophage enzyme and reduced inflammation drive brain correction of mucopolysaccharidosis IIIB by stem cell gene therapy. Brain. 2018;141:99–116.
  • Marechal V, Naffakh N, Danos O, et al. Disappearance of lysosomal storage in spleen and liver of mucopolysaccharidosis VII mice after transplantation of genetically modified bone marrow cells. Blood. 1993;82:1358–1365.
  • Hofling AA, Devine S, Vogler C, et al. Human CD34+ hematopoietic progenitor cell-directed lentiviral-mediated gene therapy in a xenotransplantation model of lysosomal storage disease. Mol Ther. 2004;9:856–865.
  • Lutzko C, Omori F, Abrams-Ogg AC, et al. Gene therapy for canine alpha-L-iduronidase deficiency: in utero adoptive transfer of genetically corrected hematopoietic progenitors results in engraftment but not amelioration of disease. Hum Gene Ther. 1999;10(9):1521–1532. DOI:10.1089/10430349950017851
  • Rothe M, Modlich U, Schambach A. Biosafety challenges for use of lentiviral vectors in gene therapy. current Gene Therapy. 2013;13(6):453–468.
  • Gomez-Ospina N, Scharenberg SG, Mostrel N, et al. Human genome-edited hematopoietic stem cells phenotypically correct Mucopolysaccharidosis type I. Nat Commun. 2019;10:4045.
  • Poletto E, Colella P, Pimentel Vera LN, et al. Improved engraftment and therapeutic efficacy by human genome-edited hematopoietic stem cells with Busulfan-based myeloablation. Mol Ther - Methods Clin Dev. 2022;25:392–409.
  • Han JF, El-Amouri SS, Dai M, et al. Getting the Most: enhancing Efficacy by Promoting Erythropoiesis and Thrombopoiesis after Gene Therapy in Mice with Hurler Syndrome. Mol Ther - Methods Clin Dev. 2018;11:52–64.
  • Dai M, Han J, El-Amouri SS, et al. Platelets are efficient and protective depots for storage, distribution, and delivery of lysosomal enzyme in mice with Hurler syndrome. Proceedings of the National Academy of Sciences. 2014;111(7):2680–2685.
  • Miwa S, Watabe AM, Shimada Y, et al. Efficient engraftment of genetically modified cells is necessary to ameliorate central nervous system involvement of murine model of mucopolysaccharidosis type II by hematopoietic stem cell targeted gene therapy. Mol Gene Metabol. 2020;130:262–273.
  • Wang D, Zhang W, Kalfa TA, et al. Reprogramming erythroid cells for lysosomal enzyme production leads to visceral and CNS cross-correction in mice with Hurler syndrome. Proceedings of the National Academy of Sciences. 2009;106(47):19958–19963.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.