RNA‐Mediated Inhibition of HIV in a Gene Therapy Setting

Abstract

At present, treatment for HIV-1 infection employs highly active anti-retroviral therapy (HAART), which utilizes a combination of RT and protease inhibitors. Unfortunately, HIV can escape many therapies because of its high mutation rate and the complexity of its pathogenesis. HIV-1 integrates into the cellular genome, which facilitates persistence and acts as a reservoir for reactivation and replication. As an alternative or adjuvant to chemotherapy we have been developing an RNA-based gene therapy approach for the treatment of HIV-1 infection. This article summarizes the various RNA based technologies that we have developed for potential application in a gene therapy setting.

Gene therapy progress and prospects: Novel gene therapy approaches for AIDS

“…Nevertheless, because RAI is not constitutively expressed in susceptible HIV-1 cells, such as CD4 T lymphocytes, macrophages, and microglial cells, its ectopic expression may render them specifically resistant to viral replication. 31 Combinations of RNA-based strategies comprising ribozymes, RNA decoys, and siRNA to efficiently block viral replication are being evaluated RNA-based gene therapy against HIV-1 includes mainly ribozymes, RNA decoys, and siRNAs (Michienzi et al 32 and references therein). Catalytic RNAs also referred to as ribozymes, aimed at disrupting transcription regulation, can be envisioned as an efficient approach for gene therapy.…”

siRNA, miRNA and HIV: promises and challenges

“…Many studies have described that HIV escapes from RNA interference through nucleotide mutations [43]. Das et al observed that long term targeting of nef sequence using a lentiviral vector which expressed a suppressive shRNA eventually selected for HIV with nucleotide mutations that escaped RNA interference [44].…”

Gene therapy progress and prospects: RNA aptamers

“…Aptamers are regarded as highly viable drug candidates because they present little of the notorious side effects associated with the current available treatments. 36,[40][41][42][43] In addition, whereas gene therapies involving ribozymes and/or Figure 2 Aptamer activity can be reversed by an antidote. Two aptamer-antidote designs have been described.…”