ArticleNature biomedical engineering2019
Immune-orthogonal orthologues of AAV capsids and of Cas9 circumvent the immune response to the administration of gene therapy.
Article in Nature biomedical engineering, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 89 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
89 citing papers in PubMed, 118 citations in OpenAlex.
- Delivery Systems for Therapeutic Genome Editing: Challenges, Innovations, and Future Perspectives.MedComm · 2026Review
- SORT LNPs encapsulating Cas9 mRNA achieve efficient editing in skeletal muscle in a dystrophic mouse model.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Inducible CRISPR/Cas systems in precision oncology: Current applications and future perspectives.Clinical and translational medicine · 2026Review
- From mechanism to medicine: CRISPR‒Cas9 delivery strategies, therapeutic applications and translation challenges.Discover nano · 2026Review
- Gene Editing Strategies for Duchenne Muscular Dystrophy: From Molecular Mechanisms to Clinical Translation.Cells · 2026Review
- Article
- Strategies for Evading Cellular Immunity Against Recombinant AAV Vectors in Gene Therapy.Current medical science · 2026Review
- Engineering programmable CAR and antigen pairing via drug-gated light activation.Nature communications · 2026Article
- The Role of CRISPR and Its Therapeutic Applications in Glioblastoma.International journal of molecular sciences · 2026Review
- Rational Immunogenicity Modulation of Virus-Like Particles by VLPIM.Computational and structural biotechnology journal · 2026Article
- Regulatable In Vivo Gene Expression via Adaptamers.bioRxiv : the preprint server for biology · 2025Article
- A review of recent studies on CRISPR/Cas9-mediated genome editing in a variety of muscle-related genetic disorders.Journal of translational medicine · 2025Review
- Brown adipocytes from pluripotent stem cells: a promising therapy for obesity.Molecular biology reports · 2025Review
- A compact base editor rescues AATD-associated liver and lung disease in mouse models.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- CRISPR-based gene therapy for huntington's disease: current advances and future prospects.Neurogenetics · 2025Review
- Nanotechnology and CRISPR/Cas-Mediated Gene Therapy Strategies: Potential Role for Treating Genetic Disorders.Molecular biotechnology · 2025Review
- Peeling back the layers of immunogenicity in Cas9-based genomic medicine.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Alveolar Epithelial Cell Dysfunction in Acute Respiratory Distress Syndrome: Mechanistic Insights and Targeted Interventions.Biomedicines · 2025Review
- Integrase-Deficient Lentiviral Vector as a Platform for Efficient CRISPR/Cas9-Mediated Gene Editing for Mucopolysaccharidosis IVA.International journal of molecular sciences · 2025Article
- Targeted in vivo gene integration of a secretion-enabled GLP-1 receptor agonist reverses diet-induced non-genetic obesity and pre-diabetes.Communications medicine · 2025Article
29 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Protein-based therapeutics can activate the adaptive immune system, leading to the production of neutralizing antibodies and the clearance of the treated cells mediated by cytotoxic T cells. Here, we show that the sequential use of immune-orthogonal orthologues of CRISPR-associated protein 9 (Cas9) and adeno-associated viruses (AAVs) evades adaptive immune responses and enables effective gene editing using repeated dosing. We compared total sequence similarities and predicted binding strengths to class-I and class-II major histocompatibility complex (MHC) proteins for 284 DNA-targeting and 84 RNA-targeting CRISPR effectors and 167 AAV VP1-capsid-protein orthologues. We predict the absence of cross-reactive immune responses for 79% of the DNA-targeting Cas orthologues-which we validated for three Cas9 orthologues in mice-yet we anticipate broad immune cross-reactivity among the AAV serotypes. We also show that efficacious in vivo gene editing is uncompromised when using multiple dosing with orthologues of AAVs and Cas9 in mice that were previously immunized against the AAV vector and the Cas9 cargo. Multiple dosing with protein orthologues may allow for sequential regimens of protein therapeutics that circumvent pre-existing immunity or induced immunity.
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.