{
  "abstract": "Despite significant medical progress, HIV-1 remains a critical global health crisis. While combination antiretroviral therapy (cART) effectively suppresses viremia, it is not curative due to the persistence of latent viral reservoirs. Autologous hematopoietic stem and progenitor cell (HSPC) gene therapy offers a promising avenue toward sustained, drug-free remission. In this study, we investigated the feasibility and safety of a multifunctional \"defend and attack\" HSPC gene therapy strategy in the pigtail macaque (Macaca nemestrina) model. The species-optimized lentiviral vector, PM-MNDU-anti-HIV-1-huEGFRt, carries four therapeutic payloads: a pigtail macaque-specific CCR5 shRNA (PM-CCR5sh1005), a CD4-based chimeric antigen receptor (D1D2CAR), a C46 fusion inhibitor peptide, and a truncated human epidermal growth factor receptor (huEGFRt) serving as a cell-surface tracking marker and anti-EGFR antibody Cetuximab (CTX)-mediated negative selection marker. Following busulfan conditioning, autologous transplantation of vector-modified HSPCs in two pigtail macaques resulted in safe hematopoietic recovery. Both animals achieved sustained, multilineage gene marking in peripheral blood and lymphoid tissues without adverse effects. In one animal, upon Simian-Human Immunodeficiency Virus (SHIV) challenge, vector-modified cells underwent robust, antigen-driven multilineage expansion across both lymphoid and myeloid compartments, which contracted during cART-induced viral suppression and rapidly rebounded following treatment interruption. Administration of CTX demonstrated partial, transient reduction in huEGFRt⁺ cells, accompanied with a reciprocal increase in plasma viral load. These findings support the feasibility of evaluating a multi-pronged anti-HIV HSPC gene therapy strategy with a negative selection marker in a non-human primate (NHP) model.",
  "abstract_shown": true,
  "affiliations": [
    "University of California Los Angeles (UCLA) AIDS Institute, Los Angeles, CA 90024, USA.",
    "UCLA Joe C. Wen School of Nursing, UCLA, Los Angeles, CA 90095, USA.",
    "Stem Cell and Gene Therapy Program, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.",
    "Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA.",
    "Department of Microbiology, Immunology, and Molecular Genetics, UCLA, Los Angeles, CA 90095, USA.",
    "Department of Medicine, University of Washington, Seattle, WA 98195, USA."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Jian Zhang"
    },
    {
      "affs": [
        2
      ],
      "name": "Jason Murray",
      "orcid": "0000-0002-5551-2607"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Wenli Mu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Surya Venugopal"
    },
    {
      "affs": [
        4
      ],
      "name": "Ella Yim"
    },
    {
      "affs": [
        2
      ],
      "name": "Teresa Einhaus",
      "orcid": "0000-0002-7048-6750"
    },
    {
      "affs": [
        2
      ],
      "name": "Stefan Radtke",
      "orcid": "0000-0002-2842-4820"
    },
    {
      "affs": [
        2,
        5
      ],
      "name": "Christopher W Peterson"
    },
    {
      "affs": [
        2,
        5
      ],
      "name": "Hans-Peter Kiem"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Dong Sung An",
      "orcid": "0000-0002-7020-9470"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bk154hz5200fd.bib",
  "cited_by": 0,
  "doi": "10.3390/v18101133",
  "fulltext_url": "https://europepmc.org/articles/PMC13709364",
  "id": "bk154hz5200fd",
  "issns": [
    "1999-4915"
  ],
  "landing_url": "https://europepmc.org/article/MED/42944053",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1311|Virus-based gene therapy research"
    ]
  ],
  "openalex": "W7221594162",
  "pdf_url": "https://europepmc.org/articles/PMC13709364?pdf=render",
  "pmcid": "PMC13709364",
  "pmid": "42944053",
  "published": "2026-10-13",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/bk154hz5200fd.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:12Z",
      "native_id": "MED:42944053",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42944053"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Virus-based gene therapy research",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Evaluation of Anti-HIV-1 HSPC-Based Gene Therapy with Negative Selection Marker in Pigtail Macaques.",
  "title_text": "Evaluation of Anti-HIV-1 HSPC-Based Gene Therapy with Negative Selection Marker in Pigtail Macaques.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:22:12Z",
  "url": "https://research.draconitic.com/paper/bk154hz5200fd",
  "venue": "Viruses",
  "versions": []
}