Lysosomal storage disease: Gene therapy on both sides of the blood-brain barrier

Molecular Genetics and Metabolism

Volumn 114, Issue 2, 2015, Pages 83-93

  Aronovich, Elena L ^a,b   Hackett, Perry B ^a,b  

^a UNIVERSITY OF MINNESOTA   (United States)

^b UNIVERSITY OF MINNESOTA MEDICAL SCHOOL   (United States)

Author keywords

Behavior; CNS; Mucopolysaccharidosis; Neurologic; Sleeping beauty transposon; Transcytosis

Indexed keywords

BIOLOGICAL MARKER; ENZYME; HYBRID PROTEIN; LENTIVIRUS VECTOR;

BLOOD BRAIN BARRIER; EXPERIMENTAL BEHAVIORAL TEST; GENE OVEREXPRESSION; GENE THERAPY; GENE VECTOR; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMAN; HURLER SYNDROME; LIVER; LYSOSOME STORAGE DISEASE; MUCOPOLYSACCHARIDOSIS; MUCOPOLYSACCHARIDOSIS TYPE IIIA; MUTAGENESIS; NERVOUS TISSUE; NONHUMAN; NONVIRAL GENE THERAPY; PRIORITY JOURNAL; PROTEIN EXPRESSION; SAFETY; SHORT SURVEY; SYSTEMIC THERAPY; VIRAL GENE THERAPY; ANIMAL; DISEASE MODEL; GENETICS; LYSOSOMAL STORAGE DISEASES; LYSOSOME; MUCOPOLYSACCHARIDOSIS I; MUCOPOLYSACCHARIDOSIS III;

ANIMALIA;

ANIMALS; BLOOD-BRAIN BARRIER; DISEASE MODELS, ANIMAL; GENETIC THERAPY; GENETIC VECTORS; HUMANS; LYSOSOMAL STORAGE DISEASES; LYSOSOMES; MUCOPOLYSACCHARIDOSIS I; MUCOPOLYSACCHARIDOSIS III;

EID: 84921803830     PISSN: 10967192     EISSN: 10967206     Source Type: Journal    
DOI: 10.1016/j.ymgme.2014.09.011     Document Type: Review

References (149)

1. Neufeld E.F., Muenzer J. The mucopolysaccharidoses. The Metabolic and Molecular Bases of Inherited Disease 2001, vol. III:3427-3436. 8th ed. C.R. Scriver (Ed.).
2. Walkley S.U. Pathogenic cascades in lysosomal disease-why so complex?. J. Inherit. Metab. Dis. 2009, 32:181-189.
3. Ohmi K., et al. Activated microglia in cortex of mouse models of mucopolysaccharidoses I and IIIB. Proc. Natl. Acad. Sci. U. S. A. 2003, 100:1902-1907.
4. Jeyakumar M., et al. Central nervous system inflammation is a hallmark of pathogenesis in mouse models of GM1 and GM2 gangliosidosis. Brain 2003, 126:974-987.
5. Archer L.D., et al. Mucopolysaccharide diseases: a complex interplay between neuroinflammation, microglial activation and adaptive immunity. J. Inherit. Metab. Dis. 2013, 36:257-262.
6. Settembre C., et al. Signals from the lysosome: a control centre for cellular clearance and energy metabolism. Nat. Rev. Mol. Cell Biol. 2013, 14:283-296.
7. Woloszynek J.C., et al. Lysosomal dysfunction results in altered energy balance. J. Biol. Chem. 2007, 282:35765-35771.
8. Vitner E.B., et al. Contribution of brain inflammation to neuronal cell death in neuronopathic forms of Gaucher's disease. Brain 2012, 135:1724-1735.
9. Beutler E. Lysosomal storage diseases: natural history and ethical and economic aspects. Mol. Genet. Metab. 2006, 88:208-215.
10. Wyatt K., et al. The effectiveness and cost-effectiveness of enzyme and substrate replacement therapies: a longitudinal cohort study of people with lysosomal storage disorders. Health Technol. Assess. 2012, 16:1-543.
11. Ponder K.P., Haskins M.E. Gene therapy for mucopolysaccharidosis. Expert Opin. Biol. Ther. 2007, 7:1333-1345.
12. Beck M. New therapeutic options for lysosomal storage disorders: enzyme replacement, small molecules and gene therapy. Hum. Genet. 2007, 121:1-22.
13. Hodges B.L., Cheng S.H. Cell and gene-based therapies for the lysosomal storage diseases. Curr. Gene Ther. 2006, 6:227-241.
14. Haskins M. Gene therapy for lysosomal storage diseases (LSDs) in large animal models. ILAR J. 2009, 50:112-121.
15. Hemsley K.M., Hopwood J.J. Lessons learnt from animal models: pathophysiology of neuropathic lysosomal storage disorders. J. Inherit. Metab. Dis. 2010, 33:363-371.
16. Fratantoni J.C., Hall C.W., Neufeld E.F. Hurler and Hunter syndromes: mutual correction of the defect in cultured fibroblasts. Science 1968, 162:570-572.
17. Kornfeld S. Trafficking of lysosomal enzymes. FASEB J. 1987, 1:462-468.
18. Brady R.O., Yang C., Zhuang Z. An innovative approach to the treatment of Gaucher disease and possibly other metabolic disorders of the brain. J. Inherit. Metab. Dis. 2013, 36:451-454.
19. Hegde R.S., Bernstein H.D. The surprising complexity of signal sequences. Trends Biochem. Sci. 2006, 31:563-571.
20. Muenzer J. Early initiation of enzyme replacement therapy for the mucopolysaccharidoses. Mol. Genet. Metab. 2014, 111:63-72.
21. Neuwelt E., et al. Strategies to advance translational research into brain barriers. Lancet Neurol. 2008, 7:84-96.
22. Whitley C.B., et al. Long-term outcome of Hurler syndrome following bone marrow transplantation. Am. J. Med. Genet. 1993, 46:209-218.
23. Krivit W., Peters C., Shapiro E.G. Bone marrow transplantation as effective treatment of central nervous system disease in globoid cell leukodystrophy, metachromatic leukodystrophy, adrenoleukodystrophy, mannosidosis, fucosidosis, aspartylglucosaminuria, Hurler, Maroteaux-Lamy, and Sly syndromes, and Gaucher disease type III. Curr. Opin. Neurol. 1999, 12:167-176.
24. Peters C., Steward C.G. Hematopoietic cell transplantation for inherited metabolic diseases: an overview of outcomes and practice guidelines. Bone Marrow Transplant. 2003, 31:229-239.
25. Krall W.J., et al. Cells expressing human glucocerebrosidase from a retroviral vector repopulate macrophages and central nervous system microglia after murine bone marrow transplantation. Blood 1994, 83:2737-2748.
26. Krivit W., et al. Microglia: the effector cell for reconstitution of the central nervous system following bone marrow transplantation for lysosomal and peroxisomal storage diseases. Cell Transplant. 1995, 4:385-392.
27. Kierdorf K., et al. Bone marrow cell recruitment to the brain in the absence of irradiation or parabiosis bias. PLoS One 2013, 8:e58544.
28. Zheng Y., et al. Treatment of the mouse model of mucopolysaccharidosis I with retrovirally transduced bone marrow. Mol. Genet. Metab. 2003, 79:233-244.
29. Biffi A., et al. Gene therapy of metachromatic leukodystrophy reverses neurological damage and deficits in mice. J. Clin. Invest. 2006, 116:3070-3082.
30. Biffi A. Genetically-modified hematopoietic stem cells and their progeny for widespread and efficient protein delivery to diseased sites: the case of lysosomal storage disorders. Curr. Gene Ther. 2012, 12:381-388.
31. Langford-Smith A., et al. Hematopoietic stem cell and gene therapy corrects primary neuropathology and behavior in mucopolysaccharidosis IIIA mice. Mol. Ther. 2012, 20:1610-1621.
32. Biffi A., et al. Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy. Science 2013, 341:1233158.
33. Boelens J.J., et al. Eurocord; Inborn Errors Working Party of European Blood and Marrow Transplant group; Duke University Blood and Marrow Transplantation Program; Centre for International Blood and Marrow Research. Blood 2013, 121:3981-3987.
34. Boelens J.J., Orchard P.J., Wynn R.F. Transplantation in inborn errors of metabolism: current considerations and future perspectives. Br. J. Haematol. 2014, [Epub ahead of print]. 10.1111/bjh.13059.
35. Yang B., et al. Global CNS transduction of adult mice by intravenously delivered rAAVrh.8 and rAAVrh.10 and nonhuman primates by rAAVrh.10. Mol. Ther. 2014, 22:1299-1309.
36. Hackett P.B., et al. Evaluating risks of insertional mutagenesis by DNA transposons in gene therapy. Transl. Res. 2013, 161:265-283.
37. Lichota J., et al. Macromolecular drug transport into the brain using targeted therapy. J. Neurochem. 2010, 113:1-13.
38. Daneman R. The blood-brain barrier in health and disease. Ann. Neurol. 2012, 72:648-672.
39. Obermeier B., Daneman R., Ransohoff R.M. Development, maintenance and disruption of the blood-brain barrier. Nat. Med. 2013, 19:1584-1596.
40. Abbott N.J. Blood-brain barrier structure and function and the challenges for CNS drug delivery. J. Inherit. Metab. Dis. 2013, 36:439-449.
41. Begley D.J., Pontikis C.C., Scarpa M. Lysosomal storage diseases and the blood-brain barrier. Curr. Pharm. Des. 2008, 14:1566-1580.
42. Muldoon L.L., et al. Immunologic privilege in the central nervous system and the blood-brain barrier. J. Cereb. Blood Flow Metab. 2013, 33:13-21.
43. Xiao G., G.L.S. Receptor-mediated endocytosis and brain delivery of therapeutic biologics. Int. J. Cell Biol. 2013, 2013:703545.
44. Urayama A., et al. Developmentally regulated mannose 6-phosphate receptor-mediated transport of a lysosomal enzyme across the blood-brain barrier. Proc. Natl. Acad. Sci. U. S. A. 2004, 101:12658-12663.
45. Urayama A., et al. Mannose 6-phosphate receptor-mediated transport of sulfamidase across the blood-brain barrier in the newborn mouse. Mol. Ther. 2008, 16:1261-1266.
46. Pardridge W.M. Drug transport across the blood-brain barrier. J. Cereb. Blood Flow Metab. 2012, 32:1959-1972.
47. Sly W.S., Vogler C. The final frontier - crossing the blood-brain barrier. EMBO Mol. Med. 2013, 5:655-657.
48. Spencer B.J., Verma I.M. Targeted delivery of proteins across the blood-brain barrier. Proc. Natl. Acad. Sci. U. S. A. 2007, 104:7594-7599.
49. Hemsley K.M., et al. Effect of high-dose, repeated intra-cerebrospinal fluid injection of sulphamidase on neuropathology in mucopolysaccharidosis type IIIA mice. Genes Brain Behav. 2008, 7:740-753.
50. Wohlfart S., Gelperina S., Kreuter J. Transport of drugs across the blood-brain barrier by nanoparticles. J. Control Release 2012, 161:264-273.
51. Watts R.J., Dennis M.S. Bispecific antibodies for delivery into the brain. Curr. Opin. Chem. Biol. 2013, 17:393-399.
52. Vogler C., et al. Overcoming the blood-brain barrier with high-dose enzyme replacement therapy in murine mucopolysaccharidosis VII. Proc. Natl. Acad. Sci. U. S. A. 2005, 102:14777-14782.
53. Ma X., et al. Improvements in mucopolysaccharidosis I mice after adult retroviral vector-mediated gene therapy with immunomodulation. Mol. Ther. 2007, 15:889-902.
54. Aronovich E.L., et al. Systemic correction of storage disease in MPS I NOD/SCID mice using the Sleeping Beauty transposon system. Mol. Ther. 2009, 17:1136-1144.
55. Lee W.C., et al. Enzyme replacement therapy results in substantial improvements in early clinical phenotype in a mouse model of globoid cell leukodystrophy. FASEB J. 2005, 19:1549-1551.
56. Blanz J., et al. Reversal of peripheral and central neural storage and ataxia after recombinant enzyme replacement therapy in alpha-mannosidosis mice. Hum. Mol. Genet. 2008, 17:3437-3445.
57. Matzner U., et al. Enzyme replacement improves nervous system pathology and function in a mouse model for metachromatic leukodystrophy. Hum. Mol. Genet. 2005, 14:1139-1152.
58. Matzner U., et al. Enzyme replacement improves ataxic gait and central nervous system histopathology in a mouse model of metachromatic leukodystrophy. Mol. Ther. 2009, 17:600-606.
59. Polito V.A., et al. Correction of CNS defects in the MPSII mouse model via systemic enzyme replacement therapy. Hum. Mol. Genet. 2010, 19:4871-4885.
60. Ou L., et al. High-dose enzyme replacement therapy in murine Hurler syndrome. Mol. Genet. Metab. 2014, 111:116-122.
61. Ivics Z., et al. Molecular reconstruction of Sleeping Beauty, a Tc1-like transposon from fish, and its transposition in human cells. Cell 1997, 91:501-510.
62. Yant S.R., et al. Somatic integration and long-term transgene expression in normal and haemophilic mice using a DNA transposon system. Nat. Genet. 2000, 25:35-41.
63. Izsvak Z., et al. Translating Sleeping Beauty transposition to molecular therapy: victories and challenges. BioEssays 2010, 32:756-767.
64. Aronovich E.L., et al. Prolonged expression of a lysosomal enzyme in mouse liver after Sleeping Beauty transposon-mediated gene delivery: implications for non-viral gene therapy of mucopolysaccharidoses. J. Gene Med. 2007, 9:403-415.
65. Chen Z.Y., et al. Minicircle DNA vectors devoid of bacterial DNA result in persistent and high-level transgene expression in vivo. Mol. Ther. 2003, 8:495-500.
66. Gracey-Maniar L.E., et al. Minicircle DNA vectors achieve sustained expression reflected by active chromatin and transcriptional level. Mol. Ther. 2013, 21:131-138.
67. Osborn M.J., et al. Minicircle DNA-based gene therapy coupled with immune modulation permits long-term expression of α-l-iduronidase in mice with mucopolysaccharidosis type I. Mol. Ther. 2011, 19:450-451.
68. Liu F., Song Y., Liu D. Hydrodynamics-based transfection in animals by systemic administration of plasmid DNA. Gene Ther. 1999, 6:1258-1266.
69. Zhang G., Budker V., Wolff J.A. High levels of foreign gene expression in hepatocytes after tail vein injections of naked plasmid DNA. Hum. Gene Ther. 1999, 10:1735-1737.
70. Bell J.B., et al. Preferential delivery of the Sleeping Beauty transposon system to livers of mice by hydrodynamic injection. Nat. Protoc. 2007, 2:3153-3165.
71. Podetz-Pedersen K., et al. Gene expression in lung and liver after intravenous infusion of polyethylenimine complexes of Sleeping Beauty transposons. Gene Ther. 2010, 21:210-220.
72. Wolfe J.H., et al. Reversal of pathology in murine mucopolysaccharidosis type VII by somatic cell gene transfer. Nature 1992, 360:749-753.
73. Traas A.M., et al. Correction of clinical manifestations of canine mucopolysacchariodsis I with neonatal retroviral vector gene therapy. Mol. Ther. 2007, 33:1423-1431.
74. Herati R.S., et al. Improved retroviral vector design results in sustained expression after adult gene therapy in mucopolysaccharidosis I mice. J. Gene Med. 2008, 10:972-982.
75. Metcalf J.A., et al. A self-inactivating gamma-retroviral vector reduces manifestations of mucopolysaccharidosis I in mice. Mol. Ther. 2010, 18:334-342.
76. Fu H., et al. Correction of neurological disease of mucopolysaccharidosis IIIB in adult mice by rAAV9 transblood-brain barrier gene delivery. Mol. Ther. 2011, 19:1025-1033.
77. Haurigot V., Bosch F. Toward a gene therapy for neurological and somatic MPSIIIA. Rare Dis. 2013, 1:e27209.
78. Hinderer C., et al. Intrathecal gene therapy corrects CNS pathology in a feline model of mucopolysaccharidosis I. Mol. Ther. 2014, 22. [Epub ahead of print]. 10.1038/mt.2014.135.
79. Haurigot V., et al. Whole body correction of mucopolysaccharidosis IIIA by intracerebrospinal fluid gene therapy. J. Clin. Invest. 2013, 123:3254-3271.
80. Gao G., et al. Clades of adeno-associated viruses are widely disseminated in human tissues. J. Virol. 2004, 78:6381-6388.
81. Foust K.D., et al. Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes. Nat. Biotechnol. 2009, 27:59-65.
82. Duque S., et al. Intravenous administration of self-complementary AAV9 enables transgene delivery to adult motor neurons. Mol. Ther. 2009, 17:1187-1196.
83. Bevan A.K., et al. Systemic gene delivery in large species for targeting spinal cord, brain, and peripheral tissues for pediatric disorders. Mol. Ther. 2011, 19:1871-1880.
84. Ruzo A., 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, 23:1237-1246.
85. Zhang H., et al. Several rAAV vectors efficiently cross the blood-brain barrier and transduce neurons and astrocytes in the neonatal mouse central nervous system. Mol. Ther. 2011, 19:1440-1448.
86. Bucher T., et al. Intracisternal delivery of AAV9 results in oligodendrocyte and motor neuron transduction in the whole central nervous system of cats. Gene Ther. 2014, 21:522-528.
87. Sabatino D.E., et al. Efficacy and safety of long-term prophylaxis in severe hemophilia a dogs following liver gene therapy using AAV vectors. Mol. Ther. 2011, 19:442-449.
88. Demaster A., et al. Long-term efficacy following readministration of an adeno-associated virus vector in dogs with glycogen storage disease type Ia. Hum. Gene Ther. 2012, 23:407-418.
89. Swain G.P., et al. Adeno-associated virus serotypes 9 and rh10 mediate strong neuronal transduction of the dog brain. Gene Ther. 2014, 21:28-36.
90. Federici T., et al. Robust spinal motor neuron transduction following intrathecal delivery of AAV9 in pigs. Gene Ther. 2012, 19:852-859.
91. Mattar C.N., et al. Systemic delivery of scAAV9 in fetal macaques facilitates neuronal transduction of the central and peripheral nervous systems. Gene Ther. 2013, 20:69-83.
92. Murrey D.A., et al. Feasibility and safety of systemic rAAV9-hNAGLU delivery for treating mucopolysaccharidosis IIIB: toxicology, biodistribution, and immunological assessments in primates. Hum. Gene Ther. Clin. Dev. 2014, 25:72-84.
93. Davidoff A.M., et al. Sex significantly influences transduction of murine liver by recombinant adeno-associated viral vectors through an androgen-dependent pathway. Blood 2003, 102:480-488.
94. Wang L., et al. Sustained correction of disease in naive and AAV2-pretreated hemophilia B dogs: AAV2/8-mediated, liver-directed gene therapy. Blood 2005, 105:3079-3086.
95. Nathwani A.C., et al. Enhancing transduction of the liver by adeno-associated viral vectors. Gene Ther. 2009, 16:60-69.
96. Ruzo A., et al. Liver production of sulfamidase reverses peripheral and ameliorates CNS pathology in mucopolysaccharidosis IIIA mice. Mol. Ther. 2012, 20:254-266.
97. Aronovich E.L., et al. Quantitative analysis of α-l-iduronidase expression in immunocompetent mice treated with the Sleeping Beauty transposon system. PLoS One 2013, 8:e78161.
98. Maguire C.A., et al. Mouse gender influences brain transduction by intravascularly administered AAV9. Mol. Ther. 2013, 21:1470-1471.
99. Nathwani A.C., et al. Adenovirus-associated virus vector-mediated gene transfer in hemophilia B. N. Engl. J. Med. 2011, 365:2357-2365.
100. Manno C.S., et al. Successful transduction of liver in hemophilia by AAV-factor IX and limitations imposed by the host immune response. Nat. Med. 2006, 12:342-347.
101. Mingozzi F., High K.A. Immune responses to AAV in clinical trials. Curr. Gene Ther. 2011, 11:321-330.
102. Mingozzi F., et al. CD8(+) T-cell responses to adeno-associated virus capsid in humans. Nat. Med. 2007, 13:419-422.
103. Rapti K., et al. Neutralizing antibodies against AAV serotypes 1, 2, 6, and 9 in sera of commonly used animal models. Mol. Ther. 2012, 20:73-83.
104. Gray S.J., et al. Global CNS gene delivery and evasion of anti-AAV-neutralizing antibodies by intrathecal AAV administration in non-human primates. Gene Ther. 2013, 20:450-459.
105. Samaranch L., et al. AAV9-mediated expression of a non-self protein in nonhuman primate central nervous system triggers widespread neuroinflammation driven by antigen-presenting cell transduction. Mol. Ther. 2014, 22:329-337.
106. Capotondo A., et al. Brain conditioning is instrumental for successful microglia reconstitution following hematopoietic stem cell transplantation. Proc. Natl. Acad. Sci. U. S. A. 2012, 109:15018-15023.
107. Bhattacharyya R., et al. A novel missense mutation in lysosomal sulfamidase is the basis of MPS III A in a spontaneous mouse mutant. Glycobiology 2001, 11:99-103.
108. Bhaumik M., et al. A mouse model for mucopolysaccharidosis type III A (Sanfilippo syndrome). Glycobiology 1999, 9:1389-1396.
109. Fraldi 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.
110. Wilkinson F.L., et al. Neuropathology in mouse models of mucopolysaccharidosis type I, IIIA and IIIB. PLoS One 2012, 7:e35787.
111. Hemsley K.M., Hopwood J.J. Development of motor deficits in a murine model of mucopolysaccharidosis type IIIA (MPS-IIIA). Behav. Brain Res. 2005, 158:191-199.
112. Ellinwood N.M., et al. Safe, efficient, and reproducible gene therapy of the brain in the dog models of Sanfilippo and Hurler syndromes. Mol. Ther. 2011, 19:251-259.
113. Baldo G., et al. Retroviral-vector-mediated gene therapy to mucopolysaccharidosis I mice improves sensorimotor impairments and other behavioral deficits. J. Inherit. Metab. Dis. 2013, 36:499-512.
114. Kirik D., et al. Reversal of motor impairments in parkinsonian rats by continuous intrastriatal delivery of l-dopa using rAAV-mediated gene transfer. Proc. Natl. Acad. Sci. U. S. A. 2002, 99:4708-4713.
115. Visigalli I., et al. Gene therapy augments the efficacy of hematopoietic cell transplantation and fully corrects mucopolysaccharidosis type I phenotype in the mouse model. Blood 2010, 116:5130-5139.
116. Schachern P.A., et al. Age-related functional and histopathological changes of the ear in the MPS I mouse. Int. J. Pediatr. Otorhinolaryngol. 2007, 71:197-203.
117. Kariya S., et al. Inner ear changes in mucopolysaccharidosis type I/Hurler syndrome. Otol. Neurotol. 2012, 33:1323-1327.
118. Chuah M.K., et al. Liver-specific transcriptional modules identified by genome-wide in silico analysis enable efficient gene therapy in mice and non-human primates. Mol. Ther. 2014, 22:1605-1613.
119. Sorrentino N.C., et al. A highly secreted sulphamidase engineered to cross the blood-brain barrier corrects brain lesions of mice with mucopolysaccharidoses type IIIA. EMBO J. Mol. Med. 2013, 5:675-690.
120. Sergijenko A., et al. Myeloid/microglial driven autologous hematopoietic stem cell gene therapy corrects a neuronopathic lysosomal disease. Mol. Ther. 2013, 21:1938-1949.
121. Wang D., et al. Engineering a lysosomal enzyme with a derivative of receptor-binding domain of apoE enables delivery across the blood-brain barrier. Proc. Natl. Acad. Sci. U. S. A. 2013, 110:2999-3004.
122. Sarkar G., et al. A carrier for non-covalent delivery of functional beta-galactosidase and antibodies against amyloid plaques and IgM to the brain. PLoS One 2011, 6:e28881.
123. Meng Y., et al. Effective intravenous therapy for neurodegenerative disease with a therapeutic enzyme and a peptide that mediates delivery to the brain. Mol. Ther. 2014, 22:547-553.
124. Kreuter J. Drug delivery to the central nervous system by polymeric nanoparticles: what do we know?. Adv. Drug Deliv. Rev. 2014, 71:2-14.
125. Couch J.A., et al. Addressing safety liabilities of TfR bispecific antibodies that cross the blood-brain barrier. Sci. Transl. Med. 2013, 5:183ra57.
126. Vogler C., et al. Transgene produces massive overexpression of human beta-glucuronidase in mice, lysosomal storage of enzyme, and strain-dependent tumors. Proc. Natl. Acad. Sci. U. S. A. 2003, 100:2669-2673.
127. Capotondo A., et al. Safety of arylsulfatase A overexpression for gene therapy of metachromatic leukodystrophy. Hum. Gene Ther. 2007, 18:821-836.
128. Gentner B., Visigalli I., L.E., Hiramatsu H., Ungari S., Giustacchini A., Schira G., Amendola M., Quattrini A., Martino S., Orlacchio A., Dick J.E., Biffi A., Naldini L. Identification of hematopoietic stem cell-specific miRNAs enables gene therapy of globoid cell leukodystrophy. Sci. Transl. Med. 2010, 2:58ra84.
129. Genovese P., et al. Targeted genome editing in human repopulating haematopoietic stem cells. Nature 2014, 510:235-240.
130. Yoshiki A., Moriwaki K. Mouse phenome research: implications of genetic background. ILAR J. 2006, 47:94-102.
131. Kraev A. Parallel universes of Black Six biology. Biol. Direct 2014, 9:18.
132. Hartman J.L., Garvik B., Hartwell L. Principles for the buffering of genetic variation. Science 2001, 291:1001-1004.
133. Erickson R.P. Mouse models of human genetic disease: which mouse is more like man?. BioEssays 1996, 18:993-998.
134. Aronovich E.L., McIvor R.S., Hackett P.B. The Sleeping Beauty transposon system: a non-viral vector for gene therapy. Hum. Mol. Genet. 2011, 20(R1):14-20.
135. Hackett P.B., et al. Efficacy and safety of Sleeping Beauty transposon-mediated gene transfer in preclinical animal studies. Curr. Gene Ther. 2011, 11:341-349.
136. Tan S., et al. Precision editing of large animal genomes. Adv. Genet. 2012, 80:37-97.
137. Reolon G.K., et al. Long-term memory for aversive training is impaired in Idua(-/-) mice, a genetic model of mucopolysaccharidosis type I. Brain Res. 2006, 1076:225-230.
138. Garcia-Rivera M., et al. Characterization of an immunodeficient mouse model of mucopolysaccharidosis type 1 suitable for preclinical testing of human stem cell and gene therapy. Brain Res. Bull. 2007, 74:429-438.
139. Pan D., et al. Progression of multiple behavioral deficits with various ages of onset in a murine model of Hurler syndrome. Brain Res. 2008, 1188:241-253.
140. Wolf D.A., et al. Direct gene transfer to the CNS prevents emergence of neurologic disease in a murine model of mucopolysaccharidosis type I. Neurobiol. Dis. 2011, 43:123-133.
141. Crawley A.C., et al. Characterization of a C57BL/6 congenic mouse strain of mucopolysaccharidosis type IIIA. Brain Res. 2006, 1104:1-17.
142. Lau A.A., et al. Open field locomotor activity and anxiety-related behaviors in mucopolysaccharidosistype IIIA mice. Behav. Brain Res. 2008, 191:130-136.
143. Naughton B.J., et al. Amyloidosis, synucleinopathy, and prion encephalopathy in a neuropathic lysosomal storage disease: the CNS-biomarker potential of peripheral blood. PLoS One 2013, 8:e80142.
144. Cesani M., et al. Metallothioneins as dynamic markers for brain disease in lysosomal disorders. Ann. Neurol. 2014, 75:127-137.
145. Scruggs B.A., et al. High-throughput screening of stem cell therapy for globoid cell leukodystrophy using automated neurophenotyping of twitcher mice. Behav. Brain Res. 2013, 236:35-47.
146. Tardieu M., et al. Intracerebral administration of AAV rh.10 carrying human SGSH and SUMF1 cDNAs in children with MPSIIIA disease: results of a phase I/II trial. Hum. Gene Ther. 2014, 25:506-516.
147. Oz G., Tkáč I., Uğurbil K. Animal models and high field imaging and spectroscopy. Dialogues Clin. Neurosci. 2013, 15:263-278.
148. Iliff J.J., et al. Brain-wide pathway for waste clearance captured by contrast-enhanced MRI. J. Clin. Invest. 2013, 123:1299-1309.
149. Van Essen D.C., et al. The WU-Minn Human Connectome Project: an overview. Neuroimage 2013, 80:62-79.