ArticleNature communications2019
Multifunctional CRISPR-Cas9 with engineered immunosilenced human T cell epitopes.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 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
124 citing papers in PubMed.
- The future of pediatric gene therapy: CRISPR-Cas9, AI, and personalized medicine.Pediatric research · 2026Review
- Pre-existing antibody and T cell responses to SaCas9, AsCas12a and CasΦ are comparable in naïve individuals.Nature communications · 2026Article
- CRISPR-based gene editing for antimicrobial resistance control in human medicine.Archives of microbiology · 2026Review
- Gene Editing Strategies for Duchenne Muscular Dystrophy: From Molecular Mechanisms to Clinical Translation.Cells · 2026Review
- Deaths in gene therapy of Duchenne muscular dystrophy and other diseases: Underlying mechanisms and mitigating strategies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- Targeted Epigenetic Activation ofBiomedicines · 2026Article
- Non-clinical safety considerations on genome editing using the CRISPR/Cas system.Genes & diseases · 2026Review
- A Translational Roadmap for Neurological Nonsense Mutation Disorders.International journal of molecular sciences · 2026Review
- Review
- CD4+ T Cells Mediate MHC-Deficient Tumor Rejection and Endothelial Cell Reprogramming.Cancer immunology research · 2026Article
- AI-driven CRISPR strategies in breast cancer: Organoid modeling, adaptive editing, and precision delivery.Iranian journal of basic medical sciences · 2026Review
- Mechanisms of and mitigating strategies for cellular immune responses to CRISPR-associated nucleases in genome editing therapy.Frontiers in medicine · 2026Review
- The Promise and Pitfalls of AAV-Mediated Gene Therapy for Duchenne Muscular Dystrophy.Current issues in molecular biology · 2025Review
- CRISPR Technology: Transforming the Future of Medicine and Diagnostics.Biochemistry · 2025Review
- Screening strategy to identify Cas9 variants with higher HDR activity based on diphtheria toxin.Journal of biomedical science · 2025Article
- Brown adipocytes from pluripotent stem cells: a promising therapy for obesity.Molecular biology reports · 2025Review
- Gene Editing Applications as Future Cardiovascular Therapies.Annual review of genetics · 2025Review
- Treating Hearing Loss: From Cochlear Implantation to Gene Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- CRISPR-based gene therapy for huntington's disease: current advances and future prospects.Neurogenetics · 2025Review
- Article
64 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
The CRISPR-Cas9 system has raised hopes for developing personalized gene therapies for complex diseases. Its application for genetic and epigenetic therapies in humans raises concerns over immunogenicity of the bacterially derived Cas9 protein. Here we detect antibodies to Streptococcus pyogenes Cas9 (SpCas9) in at least 5% of 143 healthy individuals. We also report pre-existing human CD8+T cell immunity in the majority of healthy individuals screened. We identify two immunodominant SpCas9 T cell epitopes for HLA-A*02:01 using an enhanced prediction algorithm that incorporates T cell receptor contact residue hydrophobicity and HLA binding and evaluated them by T cell assays using healthy donor PBMCs. In a proof-of-principle study, we demonstrate that Cas9 protein can be modified to eliminate immunodominant epitopes through targeted mutation while preserving its function and specificity. Our study highlights the problem of pre-existing immunity against CRISPR-associated nucleases and offers a potential solution to mitigate the T cell immune response.
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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.