GENE THERAPY FOR RHEUMATOID ARTHRITIS AIMING TELOMERASE AS A TARGET

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Telomerase is essential for the indefinite proliferation of human cells. And its activation plays a circle role in cellular immortality. We have shown that detection of telomerase activity in synovial tissues is useful for diagnosis of rheumatoid arthritis (RA). We also have shown that telomerase activity in RA synovial tissue is likely derived from infiltrating mononuclear cells and may be involved in the pathogenesis of RA and that the presence of tetomerase activity in RA may be an indicator of an aggressive phenotype.We evaluated peptide nucleic acids, (PNAS) - mediated inhibition of telomerase activity in various cell lines. The antisense PNAS against a part of telomerase gene demonstrated little inhibitory effect on telomerase activity, indicating that cellular uptake might be a limiting factor.Next, an adenovirus vector expressing antisense mRNA against a part of telomerase gene was constructed. Telomerase activities in various human cell lines infected with ,the vector were not inhibited. The result indicate that the construct of the vector needs to be further investigated.Further, an adenovirus vector expressing lipocortin 1, an endogenous anti-inflammation mediator, was constructed. A549 cells infected with the vector showed reduced prostaglandin E2 production, which indicate the vector could mimic a part of actions of corticosteroid. Further exploration for new therapeutic strategy should be continued.