Gene therapy of lysosomal storage disorders by lentiviral vectors

Alessandra Biffi, Luigi Naldini

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Lysosomal storage disorders (LSDs) comprise a class of inherited diseases characterized by disruption of normal lysosomal function and the consequent accumulation of incompletely degraded substrates. Most LSDs are caused by loss of function of specific lysosomal acid hydrolases, which act to degrade complex substrates that have been targeted for degradation after endocytosis or autophagy. The degradation occurs by a stepwise pathway, and if one step in the process fails, further degradation often ceases and the partially degraded substrate accumulates. The ensuing substrate accumulation in lysosomes affects the architecture and function of cells, tissues, and organs. In some cases, the accumulated substrate itself (as in Galactocerebrosidosis) or the product of an alternative metabolic route, which is upregulated by the accumulated primary substrate (as in the case of psycosine in Globoid Cell Leukodystrophy), is cytotoxic and leads to cell dysfunction or death. In other cases, the actual molecular mechanism triggered by the accumulated metabolite and leading to cellular toxicity and tissue pathology remains elusive.

Original languageEnglish
Title of host publicationLysosomal Storage Disorders
PublisherSpringer US
Pages133-151
Number of pages19
ISBN (Print)9780387709093, 9780387709086
DOIs
Publication statusPublished - 2007

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Gene therapy
Genetic Therapy
Globoid Cell Leukodystrophy
Autophagy
Hydrolases
Substrates
Endocytosis
Lysosomes
Pathology
Degradation
Acids
Tissue
Metabolites
Toxicity

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Gene therapy of lysosomal storage disorders by lentiviral vectors. / Biffi, Alessandra; Naldini, Luigi.

Lysosomal Storage Disorders. Springer US, 2007. p. 133-151.

Research output: Chapter in Book/Report/Conference proceedingChapter

Biffi, Alessandra ; Naldini, Luigi. / Gene therapy of lysosomal storage disorders by lentiviral vectors. Lysosomal Storage Disorders. Springer US, 2007. pp. 133-151
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