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  • Stable Transcriptional Repression and Parasitism of HIV-1

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    Morris454746Published.pdf (320.8Kb)
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    Author(s)
    Shrivastava, S
    Charlins, P
    Ackley, A
    Embree, H
    Dropulic, B
    Akkina, R
    Weinberg, MS
    Morris, KV
    Griffith University Author(s)
    Morris, Kevin V.
    Year published
    2018
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    Abstract
    Gene-based therapies represent a promising treatment for HIV-1 infection, as they offer the potential for sustained viral inhibition and reduced treatment interventions. One approach developed here involves using conditionally replicating vectors (CR-vectors). CR-vectors utilize HIV-expressed proteins to replicate and disseminate along with HIV into the budding viral particles, thereby co-infecting target cellular reservoirs. We generated and characterized several CR-vectors carrying various therapeutic payloads of non-coding RNAs targeted to HIV-1, both transcriptionally and post-transcriptionally. Both virus and vector ...
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    Gene-based therapies represent a promising treatment for HIV-1 infection, as they offer the potential for sustained viral inhibition and reduced treatment interventions. One approach developed here involves using conditionally replicating vectors (CR-vectors). CR-vectors utilize HIV-expressed proteins to replicate and disseminate along with HIV into the budding viral particles, thereby co-infecting target cellular reservoirs. We generated and characterized several CR-vectors carrying various therapeutic payloads of non-coding RNAs targeted to HIV-1, both transcriptionally and post-transcriptionally. Both virus and vector expression was followed in cell culture systems and T cells in the presence and absence of mycophenolic acid (MPA) selection. We find here that CR-vectors functionally suppress HIV expression in a long-term stable manner and that transcriptional targeting of and epigenetic silencing of HIV can be passaged to newly infected cells by the action of the CR-vector, ultimately establishing a sustained parasitism of HIV. Our findings suggest that CR-vectors with modulatory non-coding RNAs may be a viable approach to achieving long-term sustained suppression of HIV-1, leading ultimately to a functional cure.
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    Journal Title
    Molecular Therapy - Nucleic Acids
    Volume
    12
    DOI
    https://doi.org/10.1016/j.omtn.2018.04.011
    Copyright Statement
    © 2018 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
    Subject
    Biochemistry and cell biology
    Clinical sciences
    Publication URI
    http://hdl.handle.net/10072/400154
    Collection
    • Journal articles

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