Oligonucleotides attaching a reactive molecule may cause irreversible change to the target sequence at the reactive site. Inhibition of transcription, site-directed mutagenesis (or site-directed manipulation of genes) at the specific site has been proposed as a new tool of biotechnology with the use of a triplex-forming oligonucleotide. Thus, the oligonucleotides are regarded as a tool for intracellular DOS of useful reactive molecules. This review deals with development of a new alkylating group with high selectivity toward cytosine as well as new non-natural base analogs for the formation of stable non-natural triplexes.