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.