ArticleBlood advances2022
In vivo HSC transduction in rhesus macaques with an HDAd5/3+ vector targeting desmoglein 2 and transiently overexpressing cxcr4.
Article in Blood advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 29 citations in OpenAlex.
- Durable antiviral protection via directMolecular therapy. Advances · 2026Article
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- From Bench to Bedside: Ethical and Clinical Best Practices for Genome Editing Applications.International journal of molecular sciences · 2026Review
- Desmoglein 2 (DSG2)-knockout human respiratory epithelial cell model to study species B adenovirus receptor usage.Virologica Sinica · 2026Article
- In vivo gene editing of human hematopoietic stem and progenitor cells using envelope-engineered virus-like particles.Nature biotechnology · 2025Article
- Gene therapy for inborn errors of immunity: past progress, current status and future directions.Rare disease and orphan drugs journal · 2025Article
- Article
- Identifying active and inhibitor-resistant MGMT variants for gene therapy.American journal of human genetics · 2025Article
- Current and future treatments for sickle cell disease: From hematopoietic stem cell transplantation to in vivo gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Article
- Auto-expansion ofMolecular therapy. Methods & clinical development · 2024Article
- A simplified G-CSF-free procedure allows for in vivo HSC gene therapy of sickle cell disease in a mouse model.Blood advances · 2024Article
- Role of homologous recombination/recombineering on human adenovirus genome engineering: Not the only but the most competent solution.Engineering microbiology · 2024Review
- Targeted, safe, and efficient gene delivery to human hematopoietic stem and progenitor cells in vivo using the engineered AVID adenovirus vector platform.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Evolving Horizons: Adenovirus Vectors' Timeless Influence on Cancer, Gene Therapy and Vaccines.Viruses · 2023Review
- Drug delivery systems for CRISPR-based genome editors.Nature reviews. Drug discovery · 2023Review
- Swapping the serotype: A novel helper-dependent adenoviral vector platform forMolecular therapy. Methods & clinical development · 2023Article
- Mobilization-based engraftment of haematopoietic stem cells: a new perspective for chemotherapy-free gene therapy and transplantation.British medical bulletin · 2023Review
- HDAd6/35++ - A new helper-dependent adenovirus vector platform forMolecular therapy. Methods & clinical development · 2023Article
- Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
We developed a new in vivo hematopoietic stem cell (HSC) gene therapy approach that involves only IV injections and does not require myeloablation/conditioning and HSC transplantation. In this approach, HSCs are mobilized from the bone marrow into the peripheral bloodstream and transduced with IV injected helper-dependent adenovirus (HDAd) vectors. A fraction of transduced HSCs returns to the bone marrow and persists there long term. Here, we report desmoglein 2 (DSG2) as a new receptor that can be used for in vivo HSC transduction. HDAd5/3+ vectors were developed that use DSG2 as a high-affinity attachment receptor, and in vivo HSC transduction and safety after IV injection of an HDAd5/3+ vector expressing green fluorescent protein (GFP) in granulocyte colony-stimulating factor/AMD3100 (plerixafor)-mobilized rhesus macaques were studied. Unlike previously used CD46-targeting HDAd5/35++ vectors, HDAd5/3+ virions were not sequestered by rhesus erythrocytes and therefore mediated ∼10-fold higher GFP marking rates in primitive HSCs (CD34+/CD45RA-/CD90+ cells) in the bone marrow at day 7 after vector injection. To further increase the return of in vivo transduced, mobilized HSCs to the bone marrow, we transiently expressed cxcr4 in mobilized HSCs from the HDAd5/3+ vector. In vivo transduction with an HDAd5/3+GFP/cxcr4 vector at a low dose of 0.4 × 1012 viral particles/kg resulted in up to 7% of GFP-positive CD34+/CD45RA-/CD90+ cells in the bone marrow. This transduction rate is a solid basis for in vivo base or prime editing in combination with natural or drug-induced expansion of edited HSCs. Furthermore, our study provides new insights into HSC biology and trafficking after mobilization in nonhuman primates.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.