ArticleNature communications2021
Cas9-specific immune responses compromise local and systemic AAV CRISPR therapy in multiple dystrophic canine models.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
What it found
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Who cites it
109 citing papers in PubMed.
- Targeted Nanoparticle Delivery CRISPR/Cas9: overcoming biological barriers, enhancing stability, and improving therapeutic precision.International journal of pharmaceutics: X · 2026Review
- RNA delivery to the corneal endothelium using charge-altering releasable transporters.Science advances · 2026Article
- 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
- Pre-existing antibody and T cell responses to SaCas9, AsCas12a and CasΦ are comparable in naïve individuals.Nature communications · 2026Article
- Cytosine base editing of LPA in transgenic mice averts large deletions.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Decoding Undesirable Inflammatory Responses of Nucleic Acid-Delivering Lipid Nanoparticles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- High-fidelity genome and prime editing enabled by the AI-designed openCRISPR-1.Genome medicine · 2026Article
- DNA and RNA editing for the therapy of human diseases: current status, challenges, and future prospects.Molecular biomedicine · 2026Review
- Interindividual variability in immune response to AAV ocular gene delivery across species impedes immunomonitoring.JCI insight · 2026Article
- Monitoring biological effects of somatic cell genome editing.Nature reviews. Genetics · 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
- Gene Editing of Pluripotent Stem Cell-Derived Hepatic Cells for Liver Disease Modeling and Therapeutic Development.Biomolecules & therapeutics · 2026Review
- Mechanisms of and mitigating strategies for cellular immune responses to CRISPR-associated nucleases in genome editing therapy.Frontiers in medicine · 2026Review
- Canine Model of Duchenne Muscular Dystrophy.Methods in molecular biology (Clifton, N.J.) · 2026Article
- CRISPR/Cas9 in cancer therapy: clinical translation, mechanistic strategies, and therapeutic directions.Frontiers in oncology · 2026Review
- CRISPR Technology: Transforming the Future of Medicine and Diagnostics.Biochemistry · 2025Review
- A review of recent studies on CRISPR/Cas9-mediated genome editing in a variety of muscle-related genetic disorders.Journal of translational medicine · 2025Review
- Screening strategy to identify Cas9 variants with higher HDR activity based on diphtheria toxin.Journal of biomedical science · 2025Article
- Gene Editing Applications as Future Cardiovascular Therapies.Annual review of genetics · 2025Review
- High-density brush-shaped polymer lipids reduce anti-PEG antibody binding for repeated administration of mRNA therapeutics.Nature materials · 2025Article
49 more citing papers are in PubMed but not listed here.
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24 authors.
Funding
Abstract
Adeno-associated virus (AAV)-mediated CRISPR-Cas9 editing holds promise to treat many diseases. The immune response to bacterial-derived Cas9 has been speculated as a hurdle for AAV-CRISPR therapy. However, immunological consequences of AAV-mediated Cas9 expression have thus far not been thoroughly investigated in large mammals. We evaluate Cas9-specific immune responses in canine models of Duchenne muscular dystrophy (DMD) following intramuscular and intravenous AAV-CRISPR therapy. Treatment results initially in robust dystrophin restoration in affected dogs but also induces muscle inflammation, and Cas9-specific humoral and cytotoxic T-lymphocyte (CTL) responses that are not prevented by the muscle-specific promoter and transient prednisolone immune suppression. In normal dogs, AAV-mediated Cas9 expression induces similar, though milder, immune responses. In contrast, other therapeutic (micro-dystrophin and SERCA2a) and reporter (alkaline phosphatase, AP) vectors result in persistent expression without inducing muscle inflammation. Our results suggest Cas9 immunity may represent a critical barrier for AAV-CRISPR therapy in large mammals.
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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.