ArticleCell reports. Medicine2025
Senescence and inflammation are unintended adverse consequences of CRISPR-Cas9/AAV6-mediated gene editing in hematopoietic stem cells.
Article in Cell reports. Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed.
- Gero-Immunology: The critical role of aging when defining immune phenotypes.Current opinion in biomedical engineering · 2026Article
- From Gene Function to Precision Intervention: CRISPR/Cas9 and Stem Cell-Based Strategies as Emerging Disease-Modifying Approaches in PMOS.Stem cell reviews and reports · 2026Review
- SRSF2 P95H induces monocytic priming of human hematopoietic stem and progenitor cells.Leukemia · 2026Article
- In-depth characterization of stem cell potency and genotoxicity for clinical-scaleMolecular therapy. Advances · 2026Article
- Gene editing of hematopoietic stem cells: applications and advances.International journal of hematology · 2026Review
- Ex vivo expansion of hematopoietic stem and progenitor cells from human mobilized peripheral blood for gene therapy applications.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Combinatorial base editing couples disease correction with lineage amplification in hematopoietic stem and progenitor cells.bioRxiv : the preprint server for biology · 2026Article
- Evolution of Prime Editing: Enhancing Efficiency and Expanding Capacity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Nanoengineered 3D culture substrate enables superior persistence and polyclonal engraftment of genetically engineered hematopoietic stem cells.Cell stem cell · 2026Article
- Stem cell dysfunction and rejuvenation strategies in ageing: emerging advances in regenerative medicine.Frontiers in cell and developmental biology · 2026Review
- Extracellular vesicle-based delivery to airway basal cells for durable gene therapy in cystic fibrosis.Frontiers in bioengineering and biotechnology · 2026Review
- AAV-mediated gene therapy for the CNS: The case for early treatment.Molecular therapy. Methods & clinical development · 2025Article
- Article
- Engineering with care: safety assessment platforms for CRISPR-modified natural killer cells.Frontiers in immunology · 2025Review
- CRISPR/Cas9-mediated CH2 deletion of Fel d1 triggers transcriptomic reprogramming and disease-associated pathways in feline cells.Frontiers in cell and developmental biology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gene editing (GE) using homology-directed repair (HDR) in hematopoietic stem and progenitor cells (HSPCs) offers promise for long-range gene correction of inherited genetic disorders. However, cellular responses induced by CRISPR-Cas9/AAV6 engineering impair the long-term repopulating potential of HDR-edited HSPCs, adversely impacting the safety and efficacy of clinical translation. Our study uncovers a durable senescence-like response in genetically engineered HSPCs triggered by p53 and interleukin (IL)-1/nuclear factor κB (NF-κB) activation, which restricts graft size and clonal diversity in long-term transplantation assays. We show that transient p53 inhibition or blocking inflammatory pathways mitigates senescence-associated responses, improving the repopulating capacity of edited HSPCs. Importantly, we identify treatment with Anakinra, an IL-1 signaling antagonist, as a promising strategy to enhance polyclonal output in HDR-edited cells while minimizing genotoxicity risks associated with the editing procedure. Overall, our findings present strategies to overcome key hurdles in HDR-based HSPC gene therapies, providing a framework for enhancing their efficacy and safety in clinical applications.
Indexed as
Identifiers
What OpenQuestion holds
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.