Title Improved Inhibition of Human Immunodeficiency Virus Type 1 Replication by Intracellular Co-overexpression of TAR and RRE Decoys in Tandem Array
Author Seong-Wook Lee *
Address Department of Molecular Biology & Institute of Nanosensor and Biotechnology, Dankook University, Seoul 140-714, Korea
Bibliography Journal of Microbiology, 41(4),300-305, 2003,
DOI
Key Words gene therapy, HIV-1, RNA decoy, RRE, TAR
Abstract Intracellular expression of RNA decoys, such as TAR or RRE decoy, has been previously shown to protect immune cells from human immunodeficiency virus type 1 (HIV-1) replication by inhibiting the binding of the HIV-1 regulatory protein to the authentic HIV RNA sequence. However, HIV-1 challenge experiments of primary human T cells, which express the RNA decoy, demonstrated that the cells were only transiently protected, and hence, more improved protocols for HIV-1 inhibition with the RNA decoys need to be developed. In this report, in order to develop a more effective RNA decoy, we analyzed and compared the ability of a series of RNA decoy derivatives in inhibiting HIV-1 replication in CEM cells. Using an improved tRNA cassette to express high levels of RNA decoy transcripts in cells, we found that co-expression of both TAR and RRE decoys, in the form of an aligned sequence in a single transcription cassette, much more potently blocked cells from HIV-1 than the expression of only one kind of RNA decoy. This observation will have an important implication for experiments involving optimization of clinical applications in RNA decoy-based gene therapy against HIV-1.
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