Retrovirus-mediated gene transfer corrects DNA repair defect of xeroderma pigmentosum cells of complementation groups A, B and C.
With the aim to devise a long-term gene therapy protocol for skin cancers in individuals affected by the inherited autosomal recessive xeroderma pigmentosum we transferred the human DNA repair XPA, XPB/ERCC3 and XPC cDNAs, by using the recombinant retroviral vector LXSN, into primary and immortalized fibroblasts obtained from two XP-A, one XP-B (associated with Cockayne's syndrome) and two XP-C patients. After transduction, the complete correction of DNA repair deficiency and functional expression of the transgenes were monitored by UV survival, unscheduled DNA synthesis and recovery of RNA synthesis, and Western blots. The results show that the recombinant retroviruses are highly efficient vectors to transfer and stably express the human DNA repair genes in XP cells and correct the defect of DNA repair of group A, B and C. With our previous results with XPD/ERCC2, the present work extends further promising issues for the gene therapy strategy for most patients suffering from this cancer-prone syndrome.
Zeng
L
L
Laboratoire de Génétique Moléculaire, UPR 42 CNRS, Villejuif, France.
Quilliet
X
X
Chevallier-Lagente
O
O
Eveno
E
E
Sarasin
A
A
Mezzina
M
M
D015153:Blotting, Western; D018929:Cell Culture Techniques; D002648:Child; D002675:Child, Preschool; D004265:DNA Helicases; D004260:DNA Repair / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D008979:Moloney murine leukemia virus / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D014983:Xeroderma Pigmentosum / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D051760:Xeroderma Pigmentosum Group A Protein
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C497314:XPA protein, human; D051760:Xeroderma Pigmentosum Group A Protein; C072022:XPBC-ERCC-3 protein; C086984:XPC protein, human; D004265:DNA Helicases