Journal article
Engineering hematopoietic stem and progenitor cells to generate red blood cells as viral traps against HIV-1
Molecular Therapy Advances, Vol.34(3), 201799
09/10/2026
DOI: 10.1016/j.omta.2026.201799
Abstract
Canonical HIV-1 entry into target cells depends on binding to CD4 as a primary receptor. Because of this, use of the CD4 receptor as a viral trap (a decoy receptor used to prevent infection of target cells) is a promising strategy for the treatment of HIV-1. One challenge in using CD4 viral traps is maintaining enough of the decoy receptor in circulation to remain effective. Here, we present a strategy to produce cell-based CD4 viral traps by engineering hematopoietic stem and progenitor cells (HSPCs) to express the CD4 receptor in red blood cell (RBC) progeny. This takes advantage of the ability of the HSPC to repopulate the blood system for a lifetime, while leveraging the fact that RBCs greatly outnumber any cell targeted for infection. CRISPR-Cas9-engineered HSPCs efficiently express CD4 on their cell surface after differentiation to the RBC lineage in vitro. Fusion of CD4 to glycophorin A (GPA) and introduction of a truncated erythropoietin receptor (tEPOR) leads to increased CD4 expression and enrichment of edited cells (CD4-GPA-tEPOR) to levels capable of neutralizing HIV-1 pseudovirus in vitro. In sum, this work presents a potential strategy for the one-time delivery of CD4-RBC viral traps through autologous transplantation of engineered HSPCs.
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Porteus and colleagues demonstrate that human blood stem cells can be engineered such that the derived red blood cells express high levels of CD4 providing an HIV trap. This potentially durable suppressive therapy for HIV might obviate the need for patients to take anti-retroviral therapy for the rest of their lives.
Details
- Title: Subtitle
- Engineering hematopoietic stem and progenitor cells to generate red blood cells as viral traps against HIV-1
- Creators
- Sofia E. Luna - Stanford UniversityWilliam N. Feist - Stanford UniversityKaya Ben-Efraim - Stanford UniversityAlex Pendergast - Emory University School of MedicineFreja K. Ekman - Stanford UniversityBritney Hernandez-Naughton - Emory University School of MedicineMegan Merritt-Garza - Emory University School of MedicineKathleen Romero - Emory University School of MedicineZak Kostamo - Emory University School of MedicineNelson A. Amorin - Stanford UniversityNicole M. Johnston - Stanford UniversityHana Y. Ghanim - Stanford UniversityVivien Sheehan - Emory University School of MedicineAmanda M. Dudek - Stanford UniversityMatthew H. Porteus - Stanford University
- Resource Type
- Journal article
- Publication Details
- Molecular Therapy Advances, Vol.34(3), 201799
- DOI
- 10.1016/j.omta.2026.201799
- ISSN
- 3117-387X
- Publisher
- Elsevier Inc
- Grant note
- Stanford Medical Scholars Research Program American Society of Hematology Minority Medical Student Award Program Stanford Medical Scientist Training Program NIH: 1F30HL178496-01, 1F32HL154667-01, 1K99HL172253-01 Stanford T32 Graduate Training Program in Stem Cell Biology and Regenerative Medicine: 5T32GM119995 Blavatnik Family Foundation Stanford Knight-Hennessy Scholarship Paul And Daisy Soros Fellowship for New Americans Hertz Fellowship HARC Center Collab-orative Developmental Award 2024-2026: U54 AI170792 Carver College of Medicine Department of Microbiology Endowed Scholar Fund University of Iowa Sutardja Chuk Professorship in Definitive and Curative Medicine Laurie Kraus Lacob Translational Medicine endowment
We thank the NIH AIDS Reagent Repository for providing the pNL4-3 Delta EnvGFP and Global env pseudotyping panel plasmids for the HIV-1 infection experiments. We thank the Stanford Institute for Stem Cell Biology and Regenerative Medicine FACS Core for their support and access to the flow cytometry machines. We thank the Binns Program for Cord Blood Research for providing purified cord blood HSPCs. S.E.L. was supported by the Stanford Medical Scholars Research Program, the American Society of Hematology Minority Medical Student Award Program, the Stanford Medical Scientist Training Program, and NIH F30 Individual Predoctoral Fellowship (1F30HL178496-01) . W.N.F. was supported by the Stanford T32 Graduate Training Program in Stem Cell Biology and Regenerative Medicine (5T32GM119995) and the Blavatnik Family Foundation as a Blavatnik Fellow. F.K.E. was supported by the Stanford Knight-Hennessy Scholarship, Paul And Daisy Soros Fellowship for New Americans, and the Hertz Fellowship. A.M.D. was supported by NIH F32 Individual Postdoctoral Fellowship (1F32HL154667-01) , NIH K99/R00 Pathway to Independence Award (1K99HL172253-01), HARC Center Collab-orative Developmental Award 2024-2026 (Parent U54 AI170792) , and the Carver College of Medicine Department of Microbiology Endowed Scholar Fund. This work was partially supported by the University of Iowa Year 2 P3 Strategic Initiatives Program through funding received for the project entitled "High Impact Hiring Initiative (HIHI) : A Program to Strategically Recruit and Retain Talented Faculty." M.H.P. was supported by the Sutardja Chuk Professorship in Definitive and Curative Medicine and the Laurie Kraus Lacob Translational Medicine endowment.
- Language
- English
- Electronic publication date
- 06/2026
- Date published
- 09/10/2026
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9985180976502771
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