The objective of this research is to improve the efficacy of action of antisense oligonucleotides by equipping them with RNA specific cleaving agents. Recently, a series of lanthanide complexes have been designed, synthesized, and characterized by Janet Morrow and co-workers (SUNY) which catalyze the hydrolysis of the phosphodiester bond of RNA, and are inert to metal ion- dissociation in solution. Two of these metal complexes, La(S-ThP)3+ and Eu(THED)3+, will be covalently attached to an antisense oligonucleotide that targets the mutant Ha-ras transcript. The conjugates will be tested for activity in solution and cell culture assays. Improvement in activity resulting from the incorporation of this new technology into the existing repertoire of antisense technologies will encourage further development and potential commercialization of this new class of compounds for the treatment of infectious and non-infectious diseases.