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Strategic self-limiting production of infectious HIV particles by CRISPR in permissive cells.
Liu, Hong; Chen, Chen; Liao, Shuren; Sohaii, Danielle K; Cruz, Conrad R Y; Burdo, Tricia H; Cradick, Thomas J; Mehta, Anand; Barrero, Carlos; Florez, Magda; Gordon, Jennifer; Grauzam, Stephane; Dressman, James; Amini, Shohreh; Bollard, Catherine M; Kaminski, Rafal; Khalili, Kamel.
Afiliación
  • Liu H; Center for Neurovirology and Gene Editing, Department of Microbiology, Immunology, and Inflammation, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, 7th Floor, Philadelphia, PA 19140, USA.
  • Chen C; Center for Neurovirology and Gene Editing, Department of Microbiology, Immunology, and Inflammation, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, 7th Floor, Philadelphia, PA 19140, USA.
  • Liao S; Center for Neurovirology and Gene Editing, Department of Microbiology, Immunology, and Inflammation, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, 7th Floor, Philadelphia, PA 19140, USA.
  • Sohaii DK; Center for Cancer and Immunology Research, Children's National Health System, The George Washington University, 7144 13th Place NW, Washington, DC 20012, USA.
  • Cruz CRY; Center for Cancer and Immunology Research, Children's National Health System, The George Washington University, 7144 13th Place NW, Washington, DC 20012, USA.
  • Burdo TH; Center for Neurovirology and Gene Editing, Department of Microbiology, Immunology, and Inflammation, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, 7th Floor, Philadelphia, PA 19140, USA.
  • Cradick TJ; Excision Biotherapeutics, Inc., 499 Jackson Street, San Francisco, CA 94111, USA.
  • Mehta A; Department of Cell and Molecular Pharmacology, Medical University of South Carolina, Basic Science Building, Room 310, 173 Ashley Avenue, Charleston, SC 29425, USA.
  • Barrero C; Department of Pharmaceutical Sciences, School of Pharmacy, Temple University, 3307 N. Broad Street, Philadelphia, PA 19140, USA.
  • Florez M; Department of Pharmaceutical Sciences, School of Pharmacy, Temple University, 3307 N. Broad Street, Philadelphia, PA 19140, USA.
  • Gordon J; Excision Biotherapeutics, Inc., 499 Jackson Street, San Francisco, CA 94111, USA.
  • Grauzam S; Department of Cell and Molecular Pharmacology, Medical University of South Carolina, Basic Science Building, Room 310, 173 Ashley Avenue, Charleston, SC 29425, USA.
  • Dressman J; Department of Cell and Molecular Pharmacology, Medical University of South Carolina, Basic Science Building, Room 310, 173 Ashley Avenue, Charleston, SC 29425, USA.
  • Amini S; Department of Biology, College of Science and Technology, Temple University, 1900 North 12th Street, Philadelphia, PA 19122, USA.
  • Bollard CM; Center for Cancer and Immunology Research, Children's National Health System, The George Washington University, 7144 13th Place NW, Washington, DC 20012, USA.
  • Kaminski R; Center for Neurovirology and Gene Editing, Department of Microbiology, Immunology, and Inflammation, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, 7th Floor, Philadelphia, PA 19140, USA.
  • Khalili K; Center for Neurovirology and Gene Editing, Department of Microbiology, Immunology, and Inflammation, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, 7th Floor, Philadelphia, PA 19140, USA.
Mol Ther Nucleic Acids ; 32: 1010-1025, 2023 Jun 13.
Article en En | MEDLINE | ID: mdl-37346975
Post-translational glycosylation of the HIV-1 envelope protein involving precursor glycan trimming by mannosyl oligosaccharide glucosidase (MOGS) is critically important for morphogenesis of virions and viral entry. Strategic editing of the MOGS gene in T lymphocytes and myeloid origin cells harboring latent proviral DNA results in the production of non-infectious particles upon treatment of cells with latency reversal agents. Controlled activation of CRISPR-MOGS by rebound HIV-1 mitigates production of infectious particles that exhibit poor ability of the virus to penetrate uninfected cells. Moreover, exclusive activation of CRISPR in cells infected with HIV-1 alleviates concern for broad off-target impact of MOGS gene ablation in uninfected cells. Combination CRISPR treatment of peripheral blood lymphocytes prepared from blood of people with HIV-1 (PWH) tailored for editing the MOGS gene (CRISPR-MOGS) and proviral HIV-1 DNA (CRISPR-HIV) revealed a cooperative impact of CRISPR treatment in inhibiting the production of infectious HIV-1 particles. Our design for genetic inactivation of MOGS by CRISPR exhibits no detectable off-target effects on host cells or any deleterious impact on cell survival and proliferation. Our findings offer the development of a new combined gene editing-based cure strategy for the diminution of HIV-1 spread after cessation of antiretroviral therapy (ART) and its elimination.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mol Ther Nucleic Acids Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mol Ther Nucleic Acids Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos