Chemical tools for targeted mutagenesis of DNA based on triple helix formation

Abstract

The development of methods for targeted mutagenesis shows promise as an alternative form of gene therapy. Triple helix-forming oligonucleotides (TFOs) provide an attractive strategy for inducing mutations. Especially, alkylation of nucleobases with functionalized TFOs would have potential for site-directed mutation. Several studies have demonstrated that treatment of mammalian cells with TFOs can be exploited to introduce desired sequence changes and point mutations. This review summarizes targeted mutagenesis using reactive TFOs, including studies with photo reactive psolaren derivatives as well as a new reactive derivative recently developed by our group. © 2004 Pharmaceutical Society of Japan.