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Dr John Rossi - Articles and news items
Genomics, Issue 3 2011 / 20 June 2011 / Guihua Sun, Irell & Manella Graduate School of Biological Science and Department of Molecular and Cellular Biology, Beckman Research Institute of the City of Hope and John J. Rossi. Department of Molecular and Cellular Biology Beckman Research Institute of the City of Hope
Treatment and cure of human immunodeficiency virus-1(HIV-1) infection remains one of the greatest therapeutic challenges due to its persistent infection, often leading to acquired immunodeficiency syndrome (AIDS). Although it has been 28 years since the discovery of the virus, the development of an effective vaccine is still far away. Relatively newly discovered microRNAs (miRNA) are a family of small noncoding RNAs that can regulate gene expression primarily by binding to the 3’UTR of targeted transcripts. Understanding how HIV-1 infection affects the host miRNA pathway could shed some new insights related to the basic mechanisms underlying HIV-1 mediated pathologies and T-lymphocyte depletion. Here, we review literature related to the biogenesis of HIV-1 encoded miRNAs, cellular miRNAs that can directly target HIV-1 or essential cellular factors required for HIV-1 replication. We also discuss the feasibility of using miRNAs for HIV-1 therapy.
Since the first discovery of microRNA (miRNA) from C. elegans in 19931 studies of this new class of regulatory small RNA have grown rapidly and entered a new era, where they now serve as potential biomarkers and therapeutic targets in human diseases, such as cancers. Recent studies indicating that miRNAs are aberrantly expressed in cancer, are secreted by cancer cells, and are stably present in blood open a new avenue for studying cancer at the extra/intercellular level, where miRNAs serve as important cancer-released messages.
The field of oligonucleotide-based therapy experienced a revival with the discovery of RNA interference (RNAi) in 19981. RNAi is a conserved endogenous mechanism, which is triggered by double-stranded (ds) RNAs leading to target-specific inhibition of gene expression by promoting mRNA degradation or translational repression. There are two RNAi pathways that are guided either by small interfering RNAs (siRNAs), which are perfectly complementary to the mRNA or by microRNAs (miRNAs), which bind imperfectly to their target mRNA2. SiRNAs can also induce direct transcriptional gene silencing (TGS) in the nucleus, although the mechanisms underlying this are well understood in mammalian systems3,4.
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