Genetic correction of DNA repair-deficient/cancer-prone xeroderma pigmentosum group C keratinocytes

Hum Gene Ther. 2003 Jul 1;14(10):983-96. doi: 10.1089/104303403766682241.


Xeroderma pigmentosum (XP) is a rare photosensitive and cancer-prone syndrome transmitted as an autosomal recessive trait. Most cancers developed by XP patients are basal and squamous cell carcinoma strikingly restricted to sun-exposed parts of the skin. Cells from patients with classic XP are deficient in nucleotide excision repair, a versatile biochemical mechanism for removal of ultraviolet-induced DNA lesions. Among the seven classic XP complementation groups known to date (XP-A to XP-G), XP-C is the most common one in Europe and North Africa and XP-C patients remain free of neurologic problems often seen in other XP complementation groups. This has prompted us to undertake genetic correction of XP-C fibroblasts and particularly keratinocytes, which are the most relevant cells in relation to skin cancer and have proven recently to be capable of reconstructing XP-C skin in vitro. In this study, we demonstrate that DNA repair capacity, cell survival properties, and transition from proliferative to abortive keratinocyte colonies toward UVB irradiation can be fully recovered in keratinocytes from patients with XPC transduced with a retroviral vector stably driving the expression of the wild-type XPC protein. In addition, we show that in the absence of UV, XP-C keratinocytes exhibit intrinsic cell cycle abnormalities, and beta(1)-integrin overexpression, defects that are also both fully reversed after genetic correction. Together with full correction of the defects in XP-C corrected keratinocytes, in vitro reconstruction of skin from these cells open a rational perspective to XP tissue therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Division
  • Cell Survival
  • Cells, Cultured
  • Child
  • Child, Preschool
  • DNA Repair*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Genetic Complementation Test
  • Humans
  • Integrin beta1 / metabolism
  • Keratinocytes / metabolism
  • Keratinocytes / pathology*
  • Moloney murine leukemia virus / genetics
  • Skin / anatomy & histology
  • Transduction, Genetic
  • Xeroderma Pigmentosum / genetics*


  • DNA-Binding Proteins
  • Integrin beta1
  • XPC protein, human