tailieunhanh - Báo cáo khoa học: " A dual function TAR Decoy serves as an anti-HIV siRNA delivery vehicle"

A dual function TAR Decoy serves as an anti-HIV siRNA delivery vehicle | Unwalla and Rossi Virology Journal 2010 7 33 http content 7 1 33 VIROLOGY JOURNAL METHODOLOGY Open Access A dual function TAR Decoy serves as an anti-HIV siRNA delivery vehicle Hoshang J Unwalla1 John J Rossi2 Abstract The TAR RNA of HIV was engineered as an siRNA delivery vehicle to develop a combinatorial therapeutic approach. The TAR backbone was found to be a versatile backbone for expressing siRNAs. Upon expression in human cells pronounced and specific inhibition of reporter gene expression was observed with TARmiR. The resulting TARmiR construct retained its ability to bind Tat and mediate RNAi. TARmiR was able to inhibit HIV gene expression as a TAR decoy and by RNA interference when challenged with infectious proviral DNA. The implications of this dual function therapeutic would be discussed. Background Since its discovery in the eighties significant progress has been made in attempts to control HIV. Several strategies have been adopted including the use of small molecule drugs to inhibit various stages in the viral life cycle collectively called a HAART regimen. Unfortunately nearly all HIV-infected individuals on HAART will need to maintain their medications for the entirety of their lives resulting in considerable expense and sometimes the toxic side effects of these drugs. According to recent reports in the age of HAART the majority of emergency room visits by HIV-infected individuals has shifted from opportunistic infections to treatments for antiretroviral drug-related toxicities. Thus there is a clear need to develop alternative therapies to treating HIV infections. Alternative approaches to inhibit HIV have explored the use of a genetic type of therapy where HIV susceptible T-cells or stem cells that are precursors of HIV susceptible cells have been engineered to express anti-HIV molecules. These include oligonucleotide-based antivirals like siRNA ribozymes suicide genes or transdominant negative mutant proteins of HIV. Many of .