ArticleMolecular therapy : the journal of the American Society of Gene Therapy2019
Aberrant Clonal Hematopoiesis following Lentiviral Vector Transduction of HSPCs in a Rhesus Macaque.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 44 citations in OpenAlex.
- Hematologic Cancer after Gene Therapy for Cerebral Adrenoleukodystrophy.The New England journal of medicine · 2024Trial
- The Era of Gene Therapy: The Advancement of Lentiviral Vectors and Their Pseudotyping.Viruses · 2025Review
- Interlaboratory assessment of candidate reference materials for lentiviral vector copy number and integration site measurements.Molecular therapy. Methods & clinical development · 2025Article
- Packaged delivery of CRISPR-Cas9 ribonucleoproteins accelerates genome editing.Nucleic acids research · 2025Article
- Review
- Long-term tracking of haematopoietic clonal dynamics and mutations in non-human primate undergoing transplantation of lentivirally barcoded haematopoietic stem and progenitor cells.British journal of haematology · 2024Article
- Effective and stable gene transduction in rhesus macaque iPSCs capable of T-lineage differentiation utilizing the piggyBac system.Regenerative therapy · 2024Article
- Packaged delivery of CRISPR-Cas9 ribonucleoproteins accelerates genome editing.bioRxiv : the preprint server for biology · 2024Article
- In vivo gene delivery to immune cells.Current opinion in biotechnology · 2024Review
- Impact of CRISPR/HDR editing versus lentiviral transduction on long-term engraftment and clonal dynamics of HSPCs in rhesus macaques.Cell stem cell · 2024Article
- TPGS-b-PBAE Copolymer-Based Polyplex Nanoparticles for Gene Delivery and Transfection In Vivo and In Vitro.Pharmaceutics · 2024Article
- A robust knock-in approach using a minimal promoter and a minicircle.Developmental biology · 2024Article
- Meeting FDA Guidance recommendations for replication-competent virus and insertional oncogenesis testing.Molecular therapy. Methods & clinical development · 2023Review
- Clonal abundance patterns in hematopoiesis: Mathematical modeling and parameter estimation.Frontiers in systems biology · 2023Article
- INSERT-seq enables high-resolution mapping of genomically integrated DNA using Nanopore sequencing.Genome biology · 2022Article
- Article
- Clonal reconstruction from co-occurrence of vector integration sites accurately quantifies expanding clones in vivo.Nature communications · 2022Article
- The Reconstitution Dynamics of Cultivated Hematopoietic Stem Cells and Progenitors Is Independent of Age.International journal of molecular sciences · 2022Article
- Prediction and validation of hematopoietic stem and progenitor cell off-target editing in transplanted rhesus macaques.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Aberrant splicing events caused by insertion of genes of interest into expression vectors.International journal of biological sciences · 2022Article
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Authors and funding
22 authors at 6 institutions in 3 countries.
Funding
Abstract
Lentiviral vectors (LVs) are used for delivery of genes into hematopoietic stem and progenitor cells (HSPCs) in clinical trials worldwide. LVs, in contrast to retroviral vectors, are not associated with insertion site-associated malignant clonal expansions and, thus, are considered safer. Here, however, we present a case of markedly abnormal dysplastic clonal hematopoiesis affecting the erythroid, myeloid, and megakaryocytic lineages in a rhesus macaque transplanted with HSPCs that were transduced with a LV containing a strong retroviral murine stem cell virus (MSCV) constitutive promoter-enhancer in the LTR. Nine insertions were mapped in the abnormal clone, resulting in overexpression and aberrant splicing of several genes of interest, including the cytokine stem cell factor and the transcription factor PLAG1. This case represents the first clear link between lentiviral insertion-induced clonal expansion and a clinically abnormal transformed phenotype following transduction of normal primate or human HSPCs, which is concerning, and suggests that strong constitutive promoters should not be included in LVs.
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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.