Retrovirus-mediated gene transfer corrects DNA repair defect of xeroderma pigmentosum cells of complementation groups A, B and C

Abstract

With the aim to devise a long-term gene therapy protocol survival, unscheduled DNA synthesis and recovery of RNA for skin cancers in individuals affected by the inherited synthesis, and Western blots. The results show that the autosomal recessive xeroderma pigmentosum, we transrecombinant retroviruses are highly efficient vectors to ferred the human DNA repair XPA, XPB/ERCC3 and XPC transfer and stably express the human DNA repair genes cDNAs, by using the recombinant retroviral vector LXSN, in XP cells and correct the defect of DNA repair of group into primary and immortalized fibroblasts obtained from two A, B and C. With our previous results with XPD/ERCC2, XP-A, one XP-B (associated with Cockayne's syndrome) the present work extends further promising issues for the and two XP-C patients. After transduction, the complete gene therapy strategy for most patients suffering from this correction of DNA repair deficiency and functional cancer-prone syndrome. expression of the transgenes were monitored by UV

Catalase overexpression reduces UVB-induced apoptosis in a human xeroderma pigmentosum reconstructed epidermis

“…Direct gene therapy 8,[13][14][15] has been attempted successfully in vitro in XP-C. However, in vivo attempts will probably be problematic because of the complete absence of the protein in affected patients, which means that an intense immune reaction is likely in case of synthesis recovery.…”

“…12 Complementing XPC gene, direct gene therapy has been successfully attempted in vitro and showed complete correction of repair-defected cellular phenotypes. 8,[13][14][15] UVB irradiation produces two types of DNA damage: direct lesions, which are due to the absorption of photons by nucleobases; and indirect damage, which is dependent on the production of reactive oxygen species (ROS: H 2 O 2 , OH, 1 O 2 y.). [16][17][18][19][20] Several studies have shown that keratinocyte exposure to UVB irradiation generates ROS in excessive quantities that quickly overwhelm various antioxidant defense systems including non-enzymatic (a-tocopherol and vitamin C) and enzymatic antioxidants (catalase and superoxide dismutase).…”

Efficient gene transfer into human keratinocytes with recombinant adeno-associated virus vectors

“…[12][13][14][15][16] Moreover, systemic diseases such as adenosine deaminase deficiency, hemophilia A or B, and renal anemia might also be treated by transfer of a relevant therapeutic gene into the skin. 17,18 For this purpose, a vector has to provide a high transduction efficiency and sustained gene expression.…”

Nucleotide Excision Repair and Cancer

“…This could be the reason that XP-C patients suffer less from sunburn. Most abundant XP variants in human are XP-A and XP-C (~50% of all XP cases) (Zeng et al,1997). Fig.…”