A number of short modified synthetic oligodeoxynucleotides have shown promise as agents for gene therapy ( 1 – 8 ). Among these, two classes of oligonucleotides with modified backbones (the phosphorothioates [ 9 ] and methylphosphonates [ 10 ]) have emerged as primary candidates. We have synthesized another homologous type of nucleotide called a boranophosphate, or borane phosphonate ( 11 ), which can be viewed as a “hybrid” of two types of oligonucleotide molecules, i.e., the normal phosphodiester and the methylphosphonate ( see Fig. 1 ). In addition, the boranophosphate is negatively charged like the phosphorothioate, another well-studied antisense agent.

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