ArticleNature communications2023
Fertility-preserving myeloablative conditioning using single-dose CD117 antibody-drug conjugate in a rhesus gene therapy model.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
41 citing papers in PubMed, 2 syntheses or guidelines pooled it, 41 citations in OpenAlex.
- Gene Therapy for Sickle Cell Disease: Practice Recommendations from the American Society for Transplantation and Cellular Therapy and the International Society for Cell & Gene Therapy.Transplantation and cellular therapy · 2026Guideline
- Efficacy and safety of antibody-drug conjugates in the treatment of urothelial cell carcinoma: a systematic review and meta-analysis of prospective clinical trials.Frontiers in pharmacology · 2024Pooled it
- Severe inflammation and lineage skewing are associated with poor engraftment of engineered hematopoietic stem cells in patients with sickle cell disease.Nature communications · 2025Trial
- Gene therapy for hereditary hematological disorders: From clinical breakthroughs to future horizons.Molecular therapy. Nucleic acids · 2026Review
- Red lines and green lights: Gene therapy for inherited erythroid disorders beyond the haemoglobinopathies.British journal of haematology · 2026Review
- Alternative conditioning regimens for hemoglobinopathy gene therapy: balancing efficacy, toxicity, and the next frontier.Blood advances · 2026Review
- Antimetabolites synergize with non-genotoxic antibody drug conjugate conditioning in hematopoietic stem cell lentiviral gene therapy.Molecular therapy. Advances · 2026Article
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- Immune reset: what do we learn from bone marrow transplantation.Medical review (2021) · 2026Review
- CD117 epitope-shielded hematopoietic stem cell transplantation with toxin-free conditioning and in vivo selection ameliorates a β-thalassemia model.bioRxiv : the preprint server for biology · 2026Article
- Novel and emerging therapeutic strategies for clonal hematopoiesis.Haematologica · 2026Review
- Clonal dynamics, tolerance, and adverse events after CD45-ADC-conditioned autologous HSPC transplantation in macaques.Blood advances · 2026Article
- CRISPR-Cas editing technologies for viral-mediated gene therapies of human diseases: Mechanisms, progress, and challenges.Molecular therapy. Nucleic acids · 2026Review
- Engraftment of gene-edited hematopoietic stem cells after antibody-drug conjugate conditioning in nonhuman primates.Blood advances · 2026Article
- Preventing graft re-JAK-tion: safer transplant conditioning enables murine islet allograft tolerance and diabetes reversal.The Journal of clinical investigation · 2026Article
- In vivo gene editing of human hematopoietic stem and progenitor cells using envelope-engineered virus-like particles.Nature biotechnology · 2025Article
- CRISPR-based therapeutic genome editing for inherited blood disorders.Nature reviews. Drug discovery · 2025Review
- Streptavidin-drug conjugates streamline optimization of antibody-based hematopoietic stem cell transplant conditioning.Blood immunology & cellular therapy · 2025Article
- Gene therapy for inborn errors of immunity: past progress, current status and future directions.Rare disease and orphan drugs journal · 2025Article
Corrections and comments
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Authors and funding
25 authors at 3 institutions in 2 countries.
Funding
Abstract
Hematopoietic stem cell (HSC) gene therapy has curative potential; however, its use is limited by the morbidity and mortality associated with current chemotherapy-based conditioning. Targeted conditioning using antibody-drug conjugates (ADC) holds promise for reduced toxicity in HSC gene therapy. Here we test the ability of an antibody-drug conjugate targeting CD117 (CD117-ADC) to enable engraftment in a non-human primate lentiviral gene therapy model of hemoglobinopathies. Following single-dose CD117-ADC, a >99% depletion of bone marrow CD34 + CD90 + CD45RA- cells without lymphocyte reduction is observed, which results are not inferior to multi-day myeloablative busulfan conditioning. CD117-ADC, similarly to busulfan, allows efficient engraftment, gene marking, and vector-derived fetal hemoglobin induction. Importantly, ADC treatment is associated with minimal toxicity, and CD117-ADC-conditioned animals maintain fertility. In contrast, busulfan treatment commonly causes severe toxicities and infertility in humans. Thus, the myeloablative capacity of single-dose CD117-ADC is sufficient for efficient engraftment of gene-modified HSCs while preserving fertility and reducing adverse effects related to toxicity in non-human primates. This targeted conditioning approach thus provides the proof-of-principle to improve risk-benefit ratio in a variety of HSC-based gene therapy products in humans.
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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.