ArticleThe Journal of clinical investigation2024
CRISPR-Cas9 base editing of pathogenic CaMKIIδ improves cardiac function in a humanized mouse model.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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
31 citing papers in PubMed, 33 citations in OpenAlex.
- Precision modification of heart failure signaling by CRISPR-Cas9 base editing.Journal of molecular and cellular cardiology · 2026Review
- Rats develop more robust and persistent peritoneal adhesion phenotypes than mice: a multimodal comparative study.Scientific reports · 2026Article
- CRISPR and the Future of Cardiac Disease Therapy: A New Genetic Frontier.International journal of molecular sciences · 2026Review
- Ablation of PKCα Phosphorylation by CRISPR-Cas9 Base Editing Rescues Heart Failure.Circulation research · 2026Article
- Therapeutic base editing alleviates restrictive cardiomyopathy.Cell reports. Medicine · 2026Article
- Myocardial Recovery With Mechanical Circulatory Support Is Linked to Alternative Splicing and Subcellular Localization of CAMK2D.Circulation · 2026Article
- Rab14 restricts pathogens by promoting V-ATPase lysosomal delivery to drive lysosomal acidification.Nature communications · 2026Article
- Persistently increased CaMKIIδ autophosphorylation mediates pathologic SR Ca loss in a murine model of Doxorubicin-induced cardiomyopathy.Journal of molecular and cellular cardiology plus · 2026Article
- Emerging Mechanisms and Therapeutic Strategies in Dilated Cardiomyopathy.Biomedicines · 2026Review
- Beyond Lipids and Platelets: A Review of Anti-Inflammatory Strategies in Secondary Prevention of Acute Coronary Syndromes.Journal of clinical medicine · 2025Review
- LMNA-related cardiomyopathy: From molecular pathology to cardiac gene therapy.Journal of advanced research · 2025Review
- Gene Editing Applications as Future Cardiovascular Therapies.Annual review of genetics · 2025Review
- Review
- Reversing cardiac hypertrophy and heart failure using a cardiac targeting peptide linked to miRNA106a.Clinical and translational medicine · 2025Article
- Insights into the molecular mechanism of pulmonary vein stenosis in pediatric patients with congenital heart disease.JTCVS open · 2025Article
- Review
- Genetic Animal Models of Cardiovascular Pathologies.Biomedicines · 2025Review
- Cytoplasmic CaMKIIδ-B prevents myocardial recovery in heart failure.bioRxiv : the preprint server for biology · 2025Article
- Review
- Bone Marrow Niche in Cardiometabolic Disease: Mechanisms and Therapeutic Potential.Circulation research · 2025Review
Corrections and comments
- Commented on by
Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
Abstract
Cardiovascular diseases are the most common cause of worldwide morbidity and mortality, highlighting the necessity for advanced therapeutic strategies. Ca2+/calmodulin-dependent protein kinase IIδ (CaMKIIδ) is a prominent inducer of various cardiac disorders, which is mediated by 2 oxidation-sensitive methionine residues within the regulatory domain. We have previously shown that ablation of CaMKIIδ oxidation by CRISPR-Cas9 base editing enables the heart to recover function from otherwise severe damage following ischemia/reperfusion (IR) injury. Here, we extended this therapeutic concept toward potential clinical translation. We generated a humanized CAMK2D knockin mouse model in which the genomic sequence encoding the entire regulatory domain was replaced with the human sequence. This enabled comparison and optimization of two different editing strategies for the human genome in mice. To edit CAMK2D in vivo, we packaged the optimized editing components into an engineered myotropic adeno-associated virus (MyoAAV 2A), which enabled efficient delivery at a very low AAV dose into the humanized mice at the time of IR injury. CAMK2D-edited mice recovered cardiac function, showed improved exercise performance, and were protected from myocardial fibrosis, which was otherwise observed in injured control mice after IR. Our findings identify a potentially effective strategy for cardioprotection in response to oxidative damage.
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.