Construction of an adenoassociated, viral derived, expression vector to correct the genetic defect in Morquio A disease
Keywords:
Mucopolysaccharidosis IV [genetics], dependovirus, gene therapy, gene transfer techniques, virus cultivation, culture techniques
Abstract
Introduction. Mucopolysaccharidosis IVA (Morquio A) is caused by a deficiency of N-acetylgalactosamine-6-sulphate-sulphatase, a lysosomal enzyme required for the stepwise degradation of keratan-sulfate and chondroitin-6-sulfate. A deficiency in this enzyme results in an accumulation of glycosaminoglycans in several tissues. Currently, no effective therapies exist and only supportive measures are used to treat some manifestations of the disease. An ideal therapy is one that can be administrated early in life, has low mortality, and leads to long-term expression of the enzyme. Gene therapy emerges as a potential alternative to correct the genetic defect in MPS IVA. Objective. Adenoassociated virus-derived expression vectors (AAV) were constructed to correct in vitro the enzyme deficiency in mucopolysaccharidosis IVA. Materials and methods. Adenoasociated virus-derived vectors containing the human GALNS gene and driven by the citomegalivirus immedited-early promoter were constructed using a free-adenoviral protocol. HEK293 cells and human skin Morquio A fibroblasts were transfected with the recombinat vectors. Enzyme activity was measured in cells 24 and 48 hours post-transfection. Results. Free-adenovirus recombinant AAV vectors were obtained with titres up to 2.08x1010 capsids/mL. HEK293 cells and Morquio A fibroblasts transfected with vectors showed GALNS activity up to 3.05 nmoles/mg/h 48 hours post-transfection. Conclusion. The AAV mediated the in vitro expression of GALNS enzyme in the transfected cells. These results are the first step towards a gene therapy alternative to Morquio A disease using adenoassociated virus-derived vectors.Downloads
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References
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30. vanDiggelen O, Zhao H, Kleijer W, Janse H, Poorthuis B, Pelt JV, et al. A fluorometric enzyme assay for the diagnosis of Morquio type A. Clin Chem Acta. 1990;187:131-40.
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34. Aucoin MG, Perrier M, Kamen AA. Critical assessment of current adeno-associated viral vector production and quantification methods. Biotechnol Adv. 2008;26:73-88.
35. Okoyama H, Chen C. Calcium phosphate mediated gene transfer into established cell lines. En: Murray EJ, editor. Methods in molecular biology: Gene transfer and expression protocols. Clifton: The Humana Press; 1991. p. 15-20.
36. Lu Y. Recombinant adeno-associated virus as delivery vector for gene therapy-a review. Stem Cells Dev. 2004;13:133-45.
37. Ward P, Clément N, Linden M. cis effects in adeno-associated virus type 2 replication. J Virol. 2007;81: 9976-89.
38. Summerford C, Samulski RJ. Membrane-associated heparan sulfate proteoglycan is a receptor for adeno-associated virus type 2 virions. J Virol. 1998;72:1438-45.
39. Wu Z, Asokan A, Samulski R. Adeno-associated virus srotypes: vector toolkit for human gene therapy. Mol Ther. 2006;14:316-27.
40. Toietta G, Severini G, Traversari C, Tomatsu S, Sukegawa K, Fukuda S, et al. Various cells retrovirally transduced with N-acetylgalactosoamine-6-sulfate sulfatase correct Morquio skin fibroblasts in vitro. Hum Gene Ther. 2001;12:2007-16.
41. Hacein-Bey-Abina S, von Kalle C, Schmidt M, Le Deist F, Wulffraat N, McIntyre E, et al. A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. N Engl J Med. 2003;348:255-6.
42. Lewinski MK, Bushman FD. Retroviral DNA integration-mechanism and consequences. Adv Genet. 2005;55:147-81.
43. Landgrebe J, Dierks T, Schamidt B, Figura Kv. The human SUMF1 gene, required for posttranslational sulfatase modification, defines a new gene family which is conserved from pro- to eukaryotes. Gene. 2003;316:47-56.
44. Cosma M, Pepe P, Annunziata I, Newbold R, Grompe M, Parenti G, et al. The multiple sulfatase deficiency gene encodes an essential and limiting factor for the activity of sulfatases. Cell. 2003;113:445-56.
2. Montaño AM, Tomatsu S, Gottesman G, Smith M, Orii T. International Morquio A registry: Clinical manifestation and natural course of Morquio A disease. J Inherit Metab Dis. 2007;30:165-74.
3. Tomatsu S, Montaño A, Nishioka T, Gutiérrez M, Peña O, Trandafirescu G, et al. Mutation and polymorphism spectrum of the GALNS gene in mucopolysaccharidosis IVA (Morquio A). Hum Mutat. 2005;26:500-12.
4. Northover H, Cowie RA, Wraith JE. Mucopoly-saccharidosis type IVA (Morquio syndrome): a clinical review. J Inherit Metab Dis. 1996;19:357-65.
5. Cheng SH, Smith AE. Gene therapy progress and prospects: gene therapy of lysosomal storage disorders. Gene Ther. 2003;10:1275-81.
6. Tomatsu S, Fukuda M, Masue K, Sukegawa T, Fukao A, Yamagishi T, et al. Morquio disease: isolation, characterization and expression of full-length cDNA for human N-acetylgalactosamine-6-sulfate sulfatase. Biochem Biophys Res Commun. 1991;181:677-83.
7. Cooper D, Ball E, Stenson P, Phillips A, Howells K, Mort M. The Human Gene Mutation Data Base at the Institute of Medical Genetics in Cardiff. Consultado: los autores deben colocar la fecha de consulta. Disponible en: http://www.hgmd.cf.ac.uk.
8. Kato Z, Fukuda S, Tomatsu S, Vega H, Yasunaga T, Yamahishi A, et al. A Novel Common Missense Mutation G301C in the N-Acetylgalactosamine-6-sulfate Sulfatase Gene in Mucopolysaccharidosis IVA. Hum Genet. 1997;101:97-101.
9. Bernal J, Briceño I. Genetic and other diseases in the pottery of Tumaco-La Tolita culture in Colombia-Ecuador. Clin Genet. 2006;70:188-91.
10. Herzog RW, Hagstrom JN, Kung SH, Tai SJ, Wilson JM, Fisher KJ, et al. Stable gene transfer and expression of human blood coagulation factor IX after intramuscular injection of recombinant adeno-associated virus. Proc Natl Acad Sci U S A. 1997;94:5804-9.
11. Snyder RO, Miao CH, Patijn GA, Spratt SK, Danos O, Nagy D, et al. Persistent and therapeutic concentrations of human factor IX in mice after hepatic gene transfer of recombinant AAV vectors. Nat Genet. 1997;16:270-6.
12. Rutledge EA, Russell DW. Adeno-associated virus vector integration junctions. J Virol. 1997;71:8429-36.
13. Xiao W, Berta SC, Lu MM, Moscioni AD, Tazelaar J, Wilson JM. Adeno-associated virus as a vector for liver-directed gene therapy. J Virol. 1998;72:10222-6.
14. Xiao X, Li J, Samulski R. Production of high-titer recombinant adeno-associated virus vectors in the absence of helper adenovirus. J Virol. 1998;72:2224-32.
15. Fisher KJ, Kelley WM, Burda JF, Wilson JM. A novel adenovirus-adeno-associated virus hybrid vector that displays efficient rescue and delivery of the AAV genome. Hum Gene Ther. 1996;7:2079-87.
16. Vincent KA, Piraino ST, Wadsworth SC. Analysis of recombinant adeno-associated virus packaging and requirements for rep and cap gene products. J Virol. 1997;71:1897-905.
17. Samulski RJ, Chang LS, Shenk T. Helper-free stocks of recombinant adeno-associated viruses: normal integration does not require viral gene expression. J Virol. 1989;63:3822-8.
18. Sands M, Davidson B. Gene therapy for lysosomal storage diseases. Mol Ther. 2006;13:839-49.
19. Daly TM, Vogler C, Levy B, Haskins ME, Sands MS. Neonatal gene transfer leads to widespread correction of pathology in a murine model of lysosomal storage disease. Proc Natl Acad Sci USA. 1999;96:2296-300.
20. McEachern K, Nietupski J, Chuang W, Armentano D, Johnson J, Hutto E, et al. AAV8-mediated expression of glucocerebrosidase ameliorates the storage pathology in the visceral organs of a mouse model of Gaucher disease. J Gene Med. 2006;8:719-29.
21. Daly TM, Ohlemiller KK, Roberts MS, Vogler CA, Sands MS. Prevention of systemic clinical disease in MPS VII mice following AAV-mediated neonatal gene transfer. Gene Ther. 2001;8:1291-8.
22. Fraites TJ Jr, Schleissing MR, Shanely RA, Walter GA, Cloutier DA, Zolotukhin I, et al. Correction of the enzymatic and functional deficits in a model of Pompe disease using adeno-associated virus vectors. Mol Ther. 2002;5:571-8.
23. Park J, Murray GJ, Limaye A, Quirk JM, Gelderman MP, Brady RO, et al. Long-term correction of globotriaosylceramide storage in Fabry mice by recombinant adeno-associated virus-mediated gene transfer. Proc Natl Acad Sci USA. 2003;100:3450-4.
24. Hennig AK, Ogilvie JM, Ohlemiller KK, Timmers AM, Hauswirth WW, Sands MS. AAV-mediated intravitreal gene therapy reduces lysosomal storage in the retinal pigmented epithelium and improves retinal function in adult MPS VII mice. Mol Ther. 2004;10:106-116.
25. Daly TM, Okuyama T, Vogler C, Haskins ME, Muzyczka N, Sands MS. Neonatal intramuscular injection with recombinant adeno-associated virus results in prolonged beta-glucuronidase expression in situ and correction of liver pathology inmucopolysa-ccharidosis type VII mice. Hum Gene Ther. 1999;10: 85-94.
26. Ponder K, Haskins M. Gene therapy for muco- polysaccharidosis. Expert Opin Biol Ther. 2007;7: 1333-45.
27. Miwa K, Matsui K, Terabe M, Ito K, Ishida M, Takagi H, et al. Construction of novel shuttle vectors and a cosmid vector for the glutamic acid-producing bacteria Brevibacterium lactofermentum and Corynebacterium glutamicum. Gene. 1985;39:281-6.
28. Grimm D, Kern A, Pawlita M, Ferrari F, Samulski R, Kleinschmidtl J. Titration of AAV-2 particles via a novel capsid ELISA: packaging of genomes can limit production of recombinant AAV-2. Gene Ther. 1999; 6: 1322-30.
29. Russell DW, Alexander IE, Miller AD. DNA synthesis and topoisomerase inhibitors increase transduction by adeno-associated virus vectors. Proc Natl Acad Sci USA. 1995;92:5719-23.
30. vanDiggelen O, Zhao H, Kleijer W, Janse H, Poorthuis B, Pelt JV, et al. A fluorometric enzyme assay for the diagnosis of Morquio type A. Clin Chem Acta. 1990;187:131-40.
31. Barrera L, Gutierrez M, Ceron F, Garcia L. Evaluation of an episomal expression construct containing the cDNA of iduronate sulfatase in (IDS) in fibroblasts from a patient with hunter syndrome. J Inherit Metab Dis. 2002;25(Suppl.1):160.
32. Zolotukhin S. Production of recombinant adeno-associated virus vectors. Hum Gene Ther. 2005; 16: 551-7.
33. Zolotukhin S, Byrne B, Mason E, Zolotukhin I, Potter M, Chesnut K, et al. Recombinant adeno-associated virus purification using novel methods improves infectious titer and yield. Gene Ther. 1999;6:973-85.
34. Aucoin MG, Perrier M, Kamen AA. Critical assessment of current adeno-associated viral vector production and quantification methods. Biotechnol Adv. 2008;26:73-88.
35. Okoyama H, Chen C. Calcium phosphate mediated gene transfer into established cell lines. En: Murray EJ, editor. Methods in molecular biology: Gene transfer and expression protocols. Clifton: The Humana Press; 1991. p. 15-20.
36. Lu Y. Recombinant adeno-associated virus as delivery vector for gene therapy-a review. Stem Cells Dev. 2004;13:133-45.
37. Ward P, Clément N, Linden M. cis effects in adeno-associated virus type 2 replication. J Virol. 2007;81: 9976-89.
38. Summerford C, Samulski RJ. Membrane-associated heparan sulfate proteoglycan is a receptor for adeno-associated virus type 2 virions. J Virol. 1998;72:1438-45.
39. Wu Z, Asokan A, Samulski R. Adeno-associated virus srotypes: vector toolkit for human gene therapy. Mol Ther. 2006;14:316-27.
40. Toietta G, Severini G, Traversari C, Tomatsu S, Sukegawa K, Fukuda S, et al. Various cells retrovirally transduced with N-acetylgalactosoamine-6-sulfate sulfatase correct Morquio skin fibroblasts in vitro. Hum Gene Ther. 2001;12:2007-16.
41. Hacein-Bey-Abina S, von Kalle C, Schmidt M, Le Deist F, Wulffraat N, McIntyre E, et al. A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. N Engl J Med. 2003;348:255-6.
42. Lewinski MK, Bushman FD. Retroviral DNA integration-mechanism and consequences. Adv Genet. 2005;55:147-81.
43. Landgrebe J, Dierks T, Schamidt B, Figura Kv. The human SUMF1 gene, required for posttranslational sulfatase modification, defines a new gene family which is conserved from pro- to eukaryotes. Gene. 2003;316:47-56.
44. Cosma M, Pepe P, Annunziata I, Newbold R, Grompe M, Parenti G, et al. The multiple sulfatase deficiency gene encodes an essential and limiting factor for the activity of sulfatases. Cell. 2003;113:445-56.
How to Cite
1.
Barrera LA, Gutiérrez MA, García Vallejo F, Tomatsu S, Cerón F, Alméciga Díaz CJ, et al. Construction of an adenoassociated, viral derived, expression vector to correct the genetic defect in Morquio A disease. biomedica [Internet]. 2008 Sep. 1 [cited 2024 May 18];28(3):448-59. Available from: https://revistabiomedica.org/index.php/biomedica/article/view/85
Published
2008-09-01
Issue
Section
Technical note
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