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Cited by 67Lysosomal Storage Disorders ResearchVirus-based gene therapy researchCRISPR and Genetic Engineering

In utero adenine base editing corrects multi-organ pathology in a lethal lysosomal storage disease

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Bose, Sourav K., White, Brandon M., Kashyap, Meghana V., Dave, Apeksha, De Bie, Felix R., Li, Haiying, Singh, Kshitiz, Menon, Pallavi +11 more·2021·Nature Communications
DOI 10.1038/s41467-021-24443-8PMC PMC8277817
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Abstract

In utero base editing has the potential to correct disease-causing mutations before the onset of pathology. Mucopolysaccharidosis type I (MPS-IH, Hurler syndrome) is a lysosomal storage disease (LSD) affecting multiple organs, often leading to early postnatal cardiopulmonary demise. We assessed in utero adeno-associated virus serotype 9 (AAV9) delivery of an adenine base editor (ABE) targeting the Idua G→A (W392X) mutation in the MPS-IH mouse, corresponding to the common IDUA G→A (W402X) mutation in MPS-IH patients. Here we show efficient long-term W392X correction in hepatocytes and cardiomyocytes and low-level editing in the brain. In utero editing was associated with improved survival and amelioration of metabolic, musculoskeletal, and cardiac disease. This proof-of-concept study demonstrates the possibility of efficiently performing therapeutic base editing in multiple organs before birth via a clinically relevant delivery mechanism, highlighting the potential of this approach for MPS-IH and other genetic diseases.

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  • The low-level editing observed via the current approach may beneficially affect the neurobehavioral phenotype in MPS-IH, although assessment of this outcome is limited in the current study due to the lack of a strong neurobehavioral phenotype in this mouse model at the short time points assessed.

    “the low-level editing observed via the current approach may beneficially affect the neurobehavioral phenotype in MPS-IH, although assessment of this outcome is limited in the current study due to the lack of a strong neurobehavioral phenotype in this mouse model at the short time points assessed (9).”

    From Ionizable Lipid Nanoparticles for Therapeutic Base Editing of Congenital Brain Disease (2023) · cites this paper as [9]

    Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • A mouse model of MPS-IH was chosen to study LNP-mediated perinatal delivery of a gene editing therapy since the neurodevelopmental pathology in patients with this disease starts prior to or shortly after birth, is irreversible, and is resistant to currently available treatments, including enzyme replacement therapy and hematopoietic stem cell transplant.

    “In this work, a mouse model of MPS-IH was chosen to study LNP-mediated perinatal delivery of a gene editing therapy since the neurodevelopmental pathology in patients with this disease starts prior to or shortly after birth, is irreversible, and is resistant to currently available treatments, including enzyme replacement therapy and hematopoietic stem cell transplant (9).”

    From Ionizable Lipid Nanoparticles for Therapeutic Base Editing of Congenital Brain Disease (2023) · cites this paper as [9]

    Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • NGS of brain genomic DNA did not demonstrate off-target base editing above background at nine previously identified possible off-target sites for the sgRNA targeting the mouse Idua G→A mutation.

    “Next-generation sequencing of brain genomic DNA from experimental mice did not demonstrate off-target base editing above background at nine previously identified possible off-target sites for the sgRNA targeting the mouse Idua G→A mutation were assessed by NGS (9).”

    From Ionizable Lipid Nanoparticles for Therapeutic Base Editing of Congenital Brain Disease (2023) · cites this paper as [9]

    The Results report that NGS found no off-target editing above background, but the tested DNA was from liver, not brain. The Methods and Fig. 1 caption specify the top ten predicted off-target sites, not nine. The paper reports brain on-target editing separately. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • CNS targeting via prior viral vector approaches was not efficient.

    “Although encouraging, CNS targeting via these approaches was not efficient, highlighting the need to evaluate alternative delivery approaches to treat genetic CNS diseases.”

    From Ionizable Lipid Nanoparticles for Therapeutic Base Editing of Congenital Brain Disease (2023) · cites this paper as [9]

  • In utero gene editing has rescued the lethal phenotype of hereditary tyrosinemia type 1, improved the pulmonary phenotype of surfactant protein C deficiency, and ameliorated metabolic, musculoskeletal, and cardiac disease in mucopolysaccharidosis type I (MPS-IH, Hurler syndrome) in mouse models.

    “Previously, we demonstrated the therapeutic potential of in utero gene editing in mouse models of human diseases, rescuing the lethal phenotype of hereditary tyrosinemia type 1, improving the pulmonary phenotype of surfactant protein C deficiency, and ameliorating metabolic, musculoskeletal, and cardiac disease in mucopolysaccharidosis type I (MPS-IH, Hurler syndrome) (7–9).”

    From Ionizable Lipid Nanoparticles for Therapeutic Base Editing of Congenital Brain Disease (2023) · cites this paper as [9]

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  1. [1]Ferreira CR Gahl WA Lysosomal storage diseases Transl. Sci. Rare Dis. 2017 2 1 71 29152458 PMC5685203
  2. [2]Bunge S Mucopolysaccharidosis type I: identification of 8 novel mutations and determination of the frequency of the two common α-L-iduronidase mutations (W402X and Q70X) among European patients Hum. Mol. Genet. 1994 3 861 866 10.1093/hmg/3.6.861 7951228 · DOI
  3. [3]Tolar J Orchard PJ α-L-iduronidase therapy for mucopolysaccharidosis type I Biologics 2008 2 743 751 19707455 PMC2727896
  4. [4]Braunlin EA Cardiac disease in patients with mucopolysaccharidosis: presentation, diagnosis and management J. Inherit. Metab. Dis. 2011 34 1183 1197 10.1007/s10545-011-9359-8 21744090 PMC3228957 · DOI
  5. [5]Gross DM Williams JC Caprioli C Dominguez B Howell RR Echocardiographic abnormalities in the mucopolysaccharide storage diseases Am. J. Cardiol. 1988 61 170 176 10.1016/0002-9149(88)91325-2 3122547 · DOI
  6. [6]Crawfurd Md’A Early prenatal diagnosis of Hurler’s syndrome with termination of pregnancy and confirmatory findings on the fetus J. Med. Genet. 1973 10 144 153 10.1136/jmg.10.2.144 4268390 PMC1013005 · DOI
  7. [7]Crow J Gibbs DA Cozens W Spellacy E Watts RW Biochemical and histopathological studies on patients with mucopolysaccharidoses, two of whom had been treated by fibroblast transplantation J. Clin. Pathol. 1983 36 415 430 10.1136/jcp.36.4.415 6403596 PMC498237 · DOI
  8. [8]Ikeno T Prenatal diagnosis of Hurler’s syndrome—Biochemical studies on the affected fetus Hum. Genet. 1981 59 353 359 10.1007/BF00295471 6800929 · DOI
  9. [9]Weber R Spectrum and outcome of primary cardiomyopathies diagnosed during fetal life J. Am. Coll. Cardiol. Heart Fail 2014 2 403 411 25023818
  10. [10]Kiely BT Kohler JL Coletti HY Poe MD Escolar ML Early disease progression of Hurler syndrome Orphanet J. Rare Dis. 2017 12 32 10.1186/s13023-017-0583-7 28193245 PMC5307824 · DOI
  11. [11]Martin, J. J. & Ceuterick, C. Prenatal pathology in mucopolysaccharidoses: a comparison with postnatal cases. Clin Neuropathol. 2, 122–127 (1983). 6226467
  12. [12]Muenzer J Early initiation of enzyme replacement therapy for the mucopolysaccharidoses Mol. Genet. Metab. 2014 111 63 72 10.1016/j.ymgme.2013.11.015 24388732 · DOI
  13. [13]Gabrielli O Clarke LA Bruni S Coppa GV Enzyme-replacement therapy in a 5-month-old boy with attenuated presymptomatic MPS I: 5-year follow-up Pediatrics 2010 125 e183 e187 10.1542/peds.2009-1728 20026495 · DOI
  14. [14]Baldo G Enzyme replacement therapy started at birth improves outcome in difficult-to-treat organs in mucopolysaccharidosis I mice Mol. Genet. Metab. 2013 109 33 40 10.1016/j.ymgme.2013.03.005 23562162 · DOI
  15. [15]Pievani A Neonatal bone marrow transplantation prevents bone pathology in a mouse model of mucopolysaccharidosis type I Blood 2015 125 1662 1671 10.1182/blood-2014-06-581207 25298037 PMC4351510 · DOI
  16. [16]Azario I Neonatal umbilical cord blood transplantation halts skeletal disease progression in the murine model of MPS-I Sci. Rep. 2017 7 9473 10.1038/s41598-017-09958-9 28842642 PMC5573317 · DOI
  17. [17]Ahmed A Mucopolysaccharidosis (MPS) physical symptom score: development, reliability, and validity JIMD Rep. 2016 26 61 68 10.1007/8904_2015_485 26303610 PMC4864710 · DOI
  18. [18]Hartung SD Correction of metabolic, craniofacial, and neurologic abnormalities in MPS I mice treated at birth with adeno-associated virus vector transducing the human α-l-iduronidase gene Mol. Ther. 2004 9 866 875 10.1016/j.ymthe.2004.03.011 15194053 · DOI
  19. [19]Liu Y Liver-directed neonatal gene therapy prevents cardiac, bone, ear, and eye disease in mucopolysaccharidosis I mice Mol. Ther. 2005 11 35 47 10.1016/j.ymthe.2004.08.027 15585404 · DOI
  20. [20]Ou L A highly efficacious PS gene editing system corrects metabolic and neurological complications of mucopolysaccharidosis type I Mol. Ther. 2020 28 1442 1454 10.1016/j.ymthe.2020.03.018 32278382 PMC7264433 · DOI · Paper page
  21. [21]Ou L ZFN-mediated in vivo genome editing corrects murine Hurler syndrome Mol. Ther. 2019 27 178 187 10.1016/j.ymthe.2018.10.018 30528089 PMC6319315 · DOI · Paper page
  22. [22]Schuh RS Neonatal nonviral gene editing with the CRISPR/Cas9 system improves some cardiovascular, respiratory, and bone disease features of the mucopolysaccharidosis I phenotype in mice Gene Ther. 2020 27 74 84 10.1038/s41434-019-0113-4 31827259 · DOI
  23. [23]Kosicki M Tomberg K Bradley A Repair of double-strand breaks induced by CRISPR–Cas9 leads to large deletions and complex rearrangements Nat. Biotechnol. 2018 36 765 771 10.1038/nbt.4192 30010673 PMC6390938 · DOI · Paper page
  24. [26]Ryu S-M Adenine base editing in mouse embryos and an adult mouse model of Duchenne muscular dystrophy Nat. Biotechnol. 2018 36 536 539 10.1038/nbt.4148 29702637 · DOI
  25. [27]Suh S Restoration of visual function in adult mice with an inherited retinal disease via adenine base editing Nat. Biomed. Eng. 2020 5 1 10 PMC7885272 33077938
  26. [28]Endo M The developmental stage determines the distribution and duration of gene expression after early intra-amniotic gene transfer using lentiviral vectors Gene Ther. 2010 17 61 71 10.1038/gt.2009.115 19727133 · DOI
  27. [29]Stitelman DH Developmental stage determines efficiency of gene transfer to muscle satellite cells by in utero delivery of adeno-associated virus vector serotype 2/9 Mol. Ther. Methods Clin. Dev. 2014 1 14040 10.1038/mtm.2014.40 26015979 PMC4362369 · DOI
  28. [30]Stitelman DH Robust in vivo transduction of nervous system and neural stem cells by early gestational intra amniotic gene transfer using lentiviral vector Mol. Ther. 2010 18 1615 1623 10.1038/mt.2010.125 20571539 PMC2956924 · DOI
  29. [31]Ben-Zvi A Mfsd2a is critical for the formation and function of the blood–brain barrier Nature 2014 509 507 511 10.1038/nature13324 24828040 PMC4134871 · DOI · Paper page
  30. [32]Davey, M. G. et al. Induction of immune tolerance to foreign protein via adeno-associated viral vector gene transfer in mid-gestation fetal sheep. PLoS ONE12, e0171132 (2017). PMC5283730 28141818
  31. [33]Mingozzi F CD8 + T-cell responses to adeno-associated virus capsid in humans Nat. Med. 2007 13 419 422 10.1038/nm1549 17369837 · DOI · Paper page
  32. [34]Rossidis AC In utero CRISPR-mediated therapeutic editing of metabolic genes Nat. Med. 2018 24 1513 1518 10.1038/s41591-018-0184-6 30297903 PMC6249685 · DOI · Paper page
  33. [35]Sabatino DE Persistent expression of hF.IX after tolerance induction by in utero or neonatal administration of AAV-1-F.IX in hemophilia B mice Mol. Ther. 2007 15 1677 1685 10.1038/sj.mt.6300219 17565352 · DOI
  34. [38]Wang D Characterization of an MPS I-H knock-in mouse that carries a nonsense mutation analogous to the human IDUA-W402X mutation Mol. Genet. Metab. 2010 99 62 71 10.1016/j.ymgme.2009.08.002 19751987 PMC2795040 · DOI · Paper page
  35. [39]Levy JM Cytosine and adenine base editing of the brain, liver, retina, heart and skeletal muscle of mice via adeno-associated viruses Nat. Biomed. Eng. 2020 4 97 110 10.1038/s41551-019-0501-5 31937940 PMC6980783 · DOI
  36. [40]Koblan LW Improving cytidine and adenine base editors by expression optimization and ancestral reconstruction Nat. Biotechnol. 2018 36 843 846 10.1038/nbt.4172 29813047 PMC6126947 · DOI · Paper page
  37. [41]Weisstein JS Delgado E Steinbach LS Hart K Packman S Musculoskeletal manifestations of Hurler syndrome: long-term follow-up after bone marrow transplantation J. Pediatr. Orthop. 2004 24 97 101 10.1097/01241398-200401000-00019 14676543 · DOI
  38. [42]Taylor C Mobility in Hurler syndrome J. Pediatr. Orthop. 2008 28 163 168 10.1097/BPO.0b013e3181649e25 18388709 · DOI
  39. [43]Gomez-Ospina N Human genome-edited hematopoietic stem cells phenotypically correct Mucopolysaccharidosis type I Nat. Commun. 2019 10 4045 10.1038/s41467-019-11962-8 31492863 PMC6731271 · DOI
  40. [44]Gentner, B. et al. Ex-vivo gene therapy for Hurler disease: initial results from a phase I/II clinical study. Mol. Ther.27, 1 (2019).
  41. [46]Cao W Dynamics of proliferative and quiescent stem cells in liver homeostasis and injury Gastroenterology 2017 153 1133 1147 10.1053/j.gastro.2017.07.006 28716722 · DOI
  42. [47]Feldman AG Subacute liver failure following gene replacement therapy for spinal muscular atrophy type 1 J. Pediatrics 2020 225 e1 10.1016/j.jpeds.2020.05.044 PMC10152980 32473148 · DOI · Paper page
  43. [48]Shieh PB Re: “moving forward after two deaths in a gene therapy trial of myotubular myopathy” by Wilson and Flotte Hum. Gene Ther. 2020 31 787 787 10.1089/hum.2020.217 32777938 PMC7462017 · DOI · Paper page
  44. [49]Massaro G Fetal gene therapy for neurodegenerative disease of infants Nat. Med. 2018 24 1317 1323 10.1038/s41591-018-0106-7 30013199 PMC6130799 · DOI
  45. [50]Peranteau WH Correction of murine hemoglobinopathies by prenatal tolerance induction and postnatal nonmyeloablative allogeneic BM transplants Blood 2015 126 1245 1254 10.1182/blood-2015-03-636803 26124498 PMC4559936 · DOI
  46. [51]Akella RRD Kadali S Amniotic fluid glycosaminoglycans in the prenatal diagnosis of mucopolysaccharidoses—A useful biomarker Clin. Chim. Acta 2016 460 63 66 10.1016/j.cca.2016.06.021 27342998 · DOI
  47. [52]Nasr, A. A. & Fateen E. Prenatal diagnosis of mucopolysaccharidoses (MPS): the first Egyptian experience. Bratisl Lek Listy105, 310–314 (2004). 15633892
  48. [53]Wang X Mucopolysaccharidosis I mutations in Chinese patients: identification of 27 novel mutations and 6 cases involving prenatal diagnosis Clin. Genet. 2012 81 443 452 10.1111/j.1399-0004.2011.01680.x 21480867 · DOI
  49. [54]Meaney FJ Riggle SM Cunningham GC Stern KS Davis JG Prenatal genetic services: toward a national data base Clin. Obstet. Gynecol. 1993 36 510 520 10.1097/00003081-199309000-00009 8403602 · DOI
  50. [55]Akolekar R Beta J Picciarelli G Ogilvie C D’Antonio F Procedure-related risk of miscarriage following amniocentesis and chorionic villus sampling: a systematic review and meta-analysis Ultrasound Obstet. Gynecol. 2015 45 16 26 10.1002/uog.14636 25042845 · DOI
  51. [56]Zhang J Non-invasive prenatal sequencing for multiple Mendelian monogenic disorders using circulating cell-free fetal DNA Nat. Med. 2019 25 439 447 10.1038/s41591-018-0334-x 30692697 · DOI
  52. [57]Boelig MM The intravenous route of injection optimizes engraftment and survival in the murine model of in utero hematopoietic cell transplantation Biol. Blood Marrow Transplant. 2016 22 991 999 10.1016/j.bbmt.2016.01.017 26797401 · DOI
  53. [58]Zwiers C Complications of intrauterine intravascular blood transfusion: lessons learned after 1678 procedures Ultrasound Obstet. Gynecol. 2017 50 180 186 10.1002/uog.17319 27706858 PMC5601196 · DOI
  54. [60]Tomatsu S Dermatan sulfate and heparan sulfate as a biomarker for mucopolysaccharidosis I J. Inherit. Metab. Dis. 2010 33 141 150 10.1007/s10545-009-9036-3 20162367 · DOI
  55. [61]Erickson, R. P., Sandman, R. & Epstein, C. J. Lack of relationship between blood and urine levels of glycosaminoglycans and lysomal enzymes. Biochem. Med.12, 331–339 (1975). 126060
  56. [62]Saville JT McDermott BK Fuller M Glycosaminoglycan fragments as a measure of disease burden in the mucopolysaccharidosis type I mouse Mol. Genet. Metab. 2018 123 112 117 10.1016/j.ymgme.2017.12.007 29273385 · DOI
  57. [63]Fujitsuka H Biomarkers in patients with mucopolysaccharidosis type II and IV Mol. Genet. Metab. Rep. 2019 19 100455 10.1016/j.ymgmr.2019.100455 30775257 PMC6365937 · DOI
  58. [64]Khan SA Glycosaminoglycans analysis in blood and urine of patients with mucopolysaccharidosis Mol. Genet. Metab. 2018 125 44 52 10.1016/j.ymgme.2018.04.011 29779903 PMC6175648 · DOI
  59. [65]Wang J High-throughput liquid chromatography–tandem mass spectrometry quantification of glycosaminoglycans as biomarkers of mucopolysaccharidosis II Int. J. Mol. Sci. 2020 21 5449 10.3390/ijms21155449 32751752 PMC7432392 · DOI
  60. [66]Viana GM Brain pathology in mucopolysaccharidoses (MPS) patients with neurological forms J. Clin. Med. 2020 9 396 10.3390/jcm9020396 32024172 PMC7073982 · DOI
  61. [67]Prasad K-MR Xu Y Yang Z Acton ST French BA Robust cardiomyocyte-specific gene expression following systemic injection of AAV: in vivo gene delivery follows a Poisson distribution Gene Ther. 2011 18 43 52 10.1038/gt.2010.105 20703310 PMC2988989 · DOI
  62. [68]Haeussler M Evaluation of off-target and on-target scoring algorithms and integration into the guide RNA selection tool CRISPOR Genome Biol. 2016 17 148 10.1186/s13059-016-1012-2 27380939 PMC4934014 · DOI · Paper page
  63. [69]Truong D-JJ Development of an intein-mediated split–Cas9 system for gene therapy Nucleic Acids Res 2015 43 6450 6458 10.1093/nar/gkv601 26082496 PMC4513872 · DOI · Paper page
  64. [70]Gray SJ Optimizing promoters for recombinant adeno-associated virus-mediated gene expression in the peripheral and central nervous system using self-complementary vectors Hum. Gene Ther. 2011 22 1143 1153 10.1089/hum.2010.245 21476867 PMC3177952 · DOI · Paper page
  65. [73]Clement K CRISPResso2 provides accurate and rapid genome editing sequence analysis Nat. Biotechnol. 2019 37 224 226 10.1038/s41587-019-0032-3 30809026 PMC6533916 · DOI
  66. [74]Buie HR Campbell GM Klinck RJ MacNeil JA Boyd SK Automatic segmentation of cortical and trabecular compartments based on a dual threshold technique for in vivo micro-CT bone analysis Bone 2007 41 505 515 10.1016/j.bone.2007.07.007 17693147 · DOI
  67. [75]Bello-Arroyo, E. et al. MouBeAT: a new and open toolbox for guided analysis of behavioral tests in mice. Front. Behav. Neurosci. 12, 201 (2018). PMC6137138 30245618
  68. [76]Ou L Herzog TL Wilmot CM Whitley CB Standardization of α-L-iduronidase enzyme assay with Michaelis–Menten kinetics Mol. Genet. Metab. 2014 111 113 115 10.1016/j.ymgme.2013.11.009 24332804 PMC4014300 · DOI
  69. [77]Frank DB Early lineage specification defines alveolar epithelial ontogeny in the murine lung Proc. Natl Acad. Sci. USA 2019 116 4362 4371 10.1073/pnas.1813952116 30782824 PMC6410851 · DOI
  70. [78]Hama H Sca l eS: an optical clearing palette for biological imaging Nat. Neurosci. 2015 18 1518 1529 10.1038/nn.4107 26368944 · DOI

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Authors
Bose, S. K., White, B. M., Kashyap, M. V., Dave, A., De Bie, F. R., Li, H., Singh, K., Menon, P., Wang, T., Teerdhala, S., Swaminathan, V., Hartman, H. A., Jayachandran, S., Chandrasekaran, P., Musunuru, K., Jain, R., Frank, D. B., Zoltick, P., & Peranteau, W. H.
Affiliations
  • Children's Hospital of Philadelphia (US)
  • University of Pennsylvania (US)
Corresponding author
Peranteau, William H.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2021-07-13
Volume
12
Issue
1
Pages
4291-4291
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-021-24443-8
PMC
PMC8277817
OpenAlex
W3178368289
Cited by
67
References
6
Citations by year
2026: 8 · 2025: 11 · 2024: 12 · 2023: 17 · 2022: 15 · 2021: 4
FWCI
7.53
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Lirias (submittedVersion, other-oa)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • VUBIR (Vrije Universiteit Brussel) (submittedVersion)
Funders
U.S. Department of Health & Human Services | National Institutes of Health (DP2 HL152427-01)
Topics
  • Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
Keywords
adenine base editors, mucopolysaccharidosis type I, Hurler syndrome, lysosomal storage disease, AAV9 gene delivery, hepatocytes, cardiomyocytes, mouse model
MeSH terms
Animals, Disease Models, Animal, Humans, Mutation, Lysosomal Storage Diseases, Hepatocytes, Myocytes, Cardiac

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