Failure to repair the c.338C>T mutation in carnitine palmitoyl transferase 2 deficient skin fibroblasts using chimeraplasty.
Chimeraplasty, using oligonucleotides to target gene repair, was heralded as an efficient alternative approach to conventional gene therapy. We designed oligonucleotides to target a common mutation in the carnitine palmitoyl transferase 2 gene and developed a specific and sensitive assay to detect gene repair in human skin fibroblasts homozygous for the mutation. We failed to repair the gene under a variety of conditions and believe this approach is of little value until cellular DNA repair mechanisms are much better understood.
Afifi
Amal
A
Academic Unit of Child Health, University of Sheffield, Stephenson Wing, Sheffield Children's NHS Trust, Damer Street, Sheffield S10 2TH, UK.
Olpin
Simon
S
Dalton
Ann
A
Bishop
Nick
N
Grabowski
Peter S
PS
D002334:Carnitine O-Palmitoyltransferase / Q000172:deficiency / Q000235:genetics*; D002478:Cells, Cultured; D004260:DNA Repair; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D009841:Oligonucleotides / Q000494:pharmacology; D017354:Point Mutation; D012867:Skin / Q000166:cytology
D009841:Oligonucleotides; D002334:Carnitine O-Palmitoyltransferase