Many genetic disorders have recently been identified as a major cause of diseases and the regulation of gene expression has been proposed as an attractive therapeutic strategy. Synthetic oligodeoxynucleotides (ODNs) are valuable tools that interfere with gene expression by specifically binding to target genes in a sequence-specific manner. In particular, reactive ODNs are expected to be more efficient because they covalently bind to the target genes. This review summarizes the synthesis of reactive ODNs with inducible reactivity, in particular, their applications to efficient cross-linking reactions, have been developed by the author's group. We also describe applications of the cross-linking reactions to the antisense method in cells and their impact on mutagenesis in model systems.