Non-viral transfer approaches for the gene therapy of mucopolysaccharidosis type II (Hunter syndrome)

R. Tomanin, A. Friso, S. Alba, E. Piller Puicher, C. Mennuni, N. La Monica, G. Hortelano, F. Zacchello, M. Scarpa

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Aims: Hunter syndrome is a rare X-linked lysosomal storage disorder caused by the deficiency of the housekeeping enzyme iduronate-2-sulphatase (IDS). Deficiency of IDS causes accumulation of undegraded dermatan and heparan-sulphate in various tissues and organs. Approaches have been proposed for the symptomatic therapy of the disease, including bone marrow transplantation and, very recently, enzyme replacement. To date, gene therapy strategies have considered mainly retroviral and adenoviral transduction of the correct cDNA. In this paper, two non-viral somatic gene therapy approaches are proposed: encapsulated heterologous cells and muscle electro-gene transfer (EGT). Methods: Hunter primary fibroblasts were co-cultured with either cell clones overexpressing the lacking enzyme or with the same incorporated in alginate microcapsules. For EGT, plasmid vector was injected into mouse quadriceps muscle, which was then immediately electro-stimulated. Results: Co-culturing Hunter primary fibroblasts with cells over-expressing IDS resulted in a three- to fourfold increase in fibroblast enzyme activity with respect to control cells. Fibroblast IDS activity was also increased after co-culture with encapsulated cells. EGT was able to transduce genes in mouse muscle, resulting in at least a tenfold increase in IDS activity 1-5 weeks after treatment. Conclusion: Although preliminary, results from encapsulated heterologous cell clones and muscle EGT encourage further evaluations for possible application to gene therapy for Hunter syndrome.

Original languageEnglish
Pages (from-to)100-104
Number of pages5
JournalActa Paediatrica, International Journal of Paediatrics, Supplement
Volume91
Issue number439
Publication statusPublished - 2002
Externally publishedYes

Fingerprint

Mucopolysaccharidosis II
Iduronate Sulfatase
Genetic Therapy
Fibroblasts
Genes
Enzymes
Muscle Cells
Clone Cells
Dermatan Sulfate
Housekeeping
Heparitin Sulfate
Quadriceps Muscle
Coculture Techniques
Bone Marrow Transplantation
Capsules
Plasmids
Complementary DNA
Muscles
Therapeutics

Keywords

  • Electro gene transfer
  • Enzyme activity
  • Hunter syndrome
  • Iduronate-2-sulphatase
  • Microcapsules

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Tomanin, R., Friso, A., Alba, S., Piller Puicher, E., Mennuni, C., La Monica, N., ... Scarpa, M. (2002). Non-viral transfer approaches for the gene therapy of mucopolysaccharidosis type II (Hunter syndrome). Acta Paediatrica, International Journal of Paediatrics, Supplement, 91(439), 100-104.

Non-viral transfer approaches for the gene therapy of mucopolysaccharidosis type II (Hunter syndrome). / Tomanin, R.; Friso, A.; Alba, S.; Piller Puicher, E.; Mennuni, C.; La Monica, N.; Hortelano, G.; Zacchello, F.; Scarpa, M.

In: Acta Paediatrica, International Journal of Paediatrics, Supplement, Vol. 91, No. 439, 2002, p. 100-104.

Research output: Contribution to journalArticle

Tomanin, R, Friso, A, Alba, S, Piller Puicher, E, Mennuni, C, La Monica, N, Hortelano, G, Zacchello, F & Scarpa, M 2002, 'Non-viral transfer approaches for the gene therapy of mucopolysaccharidosis type II (Hunter syndrome)', Acta Paediatrica, International Journal of Paediatrics, Supplement, vol. 91, no. 439, pp. 100-104.
Tomanin, R. ; Friso, A. ; Alba, S. ; Piller Puicher, E. ; Mennuni, C. ; La Monica, N. ; Hortelano, G. ; Zacchello, F. ; Scarpa, M. / Non-viral transfer approaches for the gene therapy of mucopolysaccharidosis type II (Hunter syndrome). In: Acta Paediatrica, International Journal of Paediatrics, Supplement. 2002 ; Vol. 91, No. 439. pp. 100-104.
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AU - La Monica, N.

AU - Hortelano, G.

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