ArticleGene therapy2016
CRISPR/Cas9 DNA cleavage at SNP-derived PAM enables both in vitro and in vivo KRT12 mutation-specific targeting.
Article in Gene therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 125 citations in OpenAlex.
- Chromatin Modifications Orchestrate DNA Repair Pathway Choice: Epigenetics Strategies for Enhancing CRISPR-Cas9-Mediated Knock-In Efficiency.Cell proliferation · 2026Review
- Allele-specific suppression of pathogenic bestrophin-1 transcripts by CRISPR/Cas9-mediated genome editing.Genome medicine · 2026Article
- Anatomically Guided Non-Viral CRISPR/Cas9 Delivery in the Eye: Overcoming Barriers for Precision Gene Therapy.Pharmaceutics · 2026Review
- Meesmann Corneal Dystrophy with Epithelial Basement Membrane Abnormalities: Clinical and Genetic Analysis of Two Families with Novel and Known Mutations inInternational journal of molecular sciences · 2026Article
- Understanding exceptional response: The role of MINDY1 SNP in CDK4/6 inhibitor therapy for ERHGG advances · 2026Article
- Article
- A Novel Pathogenic Variant in theJournal of clinical medicine · 2025Article
- Peptide Nucleic Acid-Mediated Regulation of CRISPR-Cas9 Specificity.Nucleic acid therapeutics · 2024Article
- Quantifying allele-specific CRISPR editing activity with CRISPECTOR2.0.Nucleic acids research · 2024Article
- Navigating the CRISPR/Cas Landscape for Enhanced Diagnosis and Treatment of Wilson's Disease.Cells · 2024Review
- AlPaCas: allele-specific CRISPR gene editing through a protospacer-adjacent-motif (PAM) approach.Nucleic acids research · 2024Article
- Corneal gene therapy: Structural and mechanistic understanding.The ocular surface · 2023Article
- Massively parallel evaluation and computational prediction of the activities and specificities of 17 small Cas9s.Nature methods · 2023Article
- Review
- The application and progression of CRISPR/Cas9 technology in ophthalmological diseases.Eye (London, England) · 2023Review
- High-Efficiency CRISPR/Cas9-Mediated Correction of a Homozygous Mutation in Achromatopsia-Patient-Derived iPSCs.International journal of molecular sciences · 2023Article
- A highly specific CRISPR-Cas12j nuclease enables allele-specific genome editing.Science advances · 2023Article
- Allele-specific knockouts reveal a role for apontic-like in the evolutionary loss of larval melanin pigmentation in the domesticated silkworm, Bombyx mori.Insect molecular biology · 2022Article
- CRISPR/Cas systems usher in a new era of disease treatment and diagnosis.Molecular biomedicine · 2022Review
- Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
CRISPR/Cas9-based therapeutics hold the possibility for permanent treatment of genetic disease. The potency and specificity of this system has been used to target dominantly inherited conditions caused by heterozygous missense mutations through inclusion of the mutated base in the short-guide RNA (sgRNA) sequence. This research evaluates a novel approach for targeting heterozygous single-nucleotide polymorphisms (SNPs) using CRISPR/Cas9. We determined that a mutation within KRT12, which causes Meesmann's epithelial corneal dystrophy (MECD), leads to the occurrence of a novel protospacer adjacent motif (PAM). We designed an sgRNA complementary to the sequence adjacent to this SNP-derived PAM and evaluated its potency and allele specificity both in vitro and in vivo. This sgRNA was found to be highly effective at reducing the expression of mutant KRT12 mRNA and protein in vitro. To assess its activity in vivo we injected a combined Cas9/sgRNA expression construct into the corneal stroma of a humanized MECD mouse model. Sequence analysis of corneal genomic DNA revealed non-homologous end-joining repair resulting in frame-shifting deletions within the mutant KRT12 allele. This study is the first to demonstrate in vivo gene editing of a heterozygous disease-causing SNP that results in a novel PAM, further highlighting the potential for CRISPR/Cas9-based therapeutics.
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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.