ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
Predicting genotoxicity of viral vectors for stem cell gene therapy using gene expression-based machine learning.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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Who cites it
27 citing papers in PubMed, 47 citations in OpenAlex.
- SACF and GILA for in vitro transformation assessment of CRISPR/Cas9-edited cell therapy candidates: a multi-site study.Gene therapy · 2026Article
- Lentiviral rescue of UMPS auxotrophy enables drug-free selection and stable vector expression.Molecular therapy. Advances · 2026Article
- Non-viral vectors as beacons of hope for reducing genotoxic risks of gene therapy.Nature biomedical engineering · 2026Article
- Ex vivo long-term expansion of human hematopoietic stem and progenitor cells as a tool for modeling vector integration sites and clonality.Journal of translational medicine · 2026Article
- Machine Learning in Stem Cell Research: From Biological Data to Clinical Translation.Computational and structural biotechnology journal · 2026Review
- SAVI: molecular mechanisms, clinical spectrum and precision medicine approaches beyond type-I IFN.Frontiers in immunology · 2026Review
- Article
- Safety and efficacy of gene therapy for RAG1-deficient SCID.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Targeting BCL11B in CAR-engineered lymphoid progenitors drives NK-like cell development with prolonged anti-leukemic activity.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Artificial Intelligence and Computational Biology in Gene Therapy: A Review.Biochemical genetics · 2025Review
- From stem cells to pancreatic β-cells: strategies, applications, and potential treatments for diabetes.Molecular and cellular biochemistry · 2025Review
- Therapeutic antibody delivery: vector tools to boost efficacy and affordability.Frontiers in immunology · 2025Review
- Advancements in Hematopoietic Stem Cell Gene Therapy: A Journey of Progress for Viral Transduction.Cells · 2024Review
- An empowered, clinically viable hematopoietic stem cell gene therapy for the treatment of multisystemic mucopolysaccharidosis type II.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Using A Google Web Search Analysis to Assess the Utility of ChatGPT in Stem Cell Therapy.Stem cells translational medicine · 2024Article
- Preclinical toxicity analyses of lentiviral vectors expressing the HIV-1 LTR-specific designer-recombinase Brec1.PloS one · 2024Article
- Third-generation lentiviral gene therapy rescues function in a mouse model of Usher 1B.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Gene and Cellular Therapies for Leukodystrophies.Pharmaceutics · 2023Review
- Development of anMolecular therapy. Methods & clinical development · 2023Article
- TGFCells · 2023Article
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 5 countries.
Funding
Abstract
Hematopoietic stem cell gene therapy is emerging as a promising therapeutic strategy for many diseases of the blood and immune system. However, several individuals who underwent gene therapy in different trials developed hematological malignancies caused by insertional mutagenesis. Preclinical assessment of vector safety remains challenging because there are few reliable assays to screen for potential insertional mutagenesis effects in vitro. Here we demonstrate that genotoxic vectors induce a unique gene expression signature linked to stemness and oncogenesis in transduced murine hematopoietic stem and progenitor cells. Based on this finding, we developed the surrogate assay for genotoxicity assessment (SAGA). SAGA classifies integrating retroviral vectors using machine learning to detect this gene expression signature during the course of in vitro immortalization. On a set of benchmark vectors with known genotoxic potential, SAGA achieved an accuracy of 90.9%. SAGA is more robust and sensitive and faster than previous assays and reliably predicts a mutagenic risk for vectors that led to leukemic severe adverse events in clinical trials. Our work provides a fast and robust tool for preclinical risk assessment of gene therapy vectors, potentially paving the way for safer gene therapy trials.
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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.