Delivery of double-stranded DNA thioaptamers into HIV-1 infected cells for antiviral activity.

Biochemical and Biophysical Research Communications
Monique R FergusonDavid G Gorenstein

Abstract

Oligonucleotide agents (ODN) are emerging as attractive alternatives to chemical drugs. However, the clinical use of ODNs as therapeutics has been hindered by their susceptibility to degradation by cellular enzymes and their limited ability to penetrate intact cells. We have used various liposome-mediated transfection agents, for the in vitro delivery of DNA thioaptamers into U373-MAGI-CCR5 cells. Our lead thioaptamer, R12-2, targets the RNase H domain of the HIV-1 reverse transcriptase (RT) and inhibits viral infection in U373-MAGI-CCR5 cells. R12-2, a 62-base-pair, double-stranded DNA molecule with a monothio-phosphate modified backbone, was selected through a novel combinatorial selection method. We studied the use of oligofectamine (OF), TFX-20, Transmessenger (TM), and Gene Jammer (GJ) for transfection of the thio-modified DNA aptamers. OF-transfected U373-MAGI-CCR5 cells resulted in 68% inhibition of HIV infection in the treated cells compared to the untreated control. Inhibition was observed in a dose-dependent manner with maximal inhibition of 83%. In this report, we demonstrate that monothioate-modified DNA duplex oligonucleotides can be efficiently delivered into cells by liposome-based transfection agents to inhibit ...Continue Reading

References

Aug 30, 1990·Nature·A D Ellington, J W Szostak
Apr 4, 1989·Biochemistry·J F Milligan, O C Uhlenbeck
Jan 1, 1995·Annual Review of Biochemistry·L GoldM Yarus
Mar 12, 1993·Science·W S Marshall, M H Caruthers
Jan 5, 2002·Journal of Controlled Release : Official Journal of the Controlled Release Society·Feng Liu, Leaf Huang
Sep 3, 2002·Advanced Drug Delivery Reviews·Thomas MerdanThomas Kissel
Sep 12, 2002·Clinical Pharmacokinetics·Cathryn MahTerence R Flotte
Sep 9, 2005·The AAPS Journal·Siddhesh D PatilDiane J Burgess

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Citations

Dec 15, 2006·Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology·David H Dreyfus
Jul 22, 2008·Oligonucleotides·Jeffrey J DeStefano, Gauri R Nair
Jun 14, 2014·European Journal of Medicinal Chemistry·Liang Xu Keliang Liu
Jul 14, 2017·Biomedicines·David E Volk, Ganesh L R Lokesh
Jul 31, 2013·Antimicrobial Agents and Chemotherapy·Liang XuKeliang Liu
Sep 2, 2016·Current Protocols in Nucleic Acid Chemistry·Xianbin Yang
Sep 19, 2017·Current Protocols in Nucleic Acid Chemistry·Xianbin Yang
Jan 20, 2007·Biochemical Society Transactions·V ThiviyanathanD G Gorenstein

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