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[Drug delivery system (DDS) for the use of antisense oligodeoxynucleotide phosphorothioate in controlling gene
N Maeda1, N Miyano-Kurosaki, N Yamamoto
1Department of Molecular Virology and Microbiology, School of Medicine, Tokyo Medical and Dental University.
Abstract:
Synthetic antisense oligodeoxynucleotide phosphorothioates (ODNs) are widely used as therapeutic tools in various in vitro and in vivo systems. Here, we applied ODNs to inhibit viral gene expression. Human T-cell leukemia virus type I (HTLV-I) is a retrovirus, and is closely linked to adult T-cell leukemia (ATL), HTLV-I-associated myelopathy/tropical spastic paraparesis(HAM/TSP), and other HTLV-I-associated diseases. With an attempt to control viral replication in vitro, ODNs to HTLV-I tax gene were synthesized and applied. In addition, 1,2-dioleoyloxy-3-(trimethylammonio) propane, DOTAP as a drug delivery system, was exploited to increase the cellular uptake of ODNs. Combination of ODNs and DOTAP was more effective to suppress viral antigen expression than ODNs only. Therefore this combination method may be useful in clinical trials for HTLV-I-associated diseases.