ArticleScientific reports2017
Towards personalised allele-specific CRISPR gene editing to treat autosomal dominant disorders.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed.
- Precise CRISPR-Mediated Editing of theInternational journal of molecular sciences · 2026Article
- Haplotype editing with CRISPR-Cas9 as a therapeutic approach for dominant-negative missense mutations in NEFL.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Structure-Guided Engineering of a Cas12i Nuclease Unlocks Near-PAMless Genome Editing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- CRISPR Base Editing Correction of TGFBI Mutations in Autosomal Dominant Corneal Dystrophies.Investigative ophthalmology & visual science · 2026Article
- Customizing CRISPR-Cas PAM specificity with protein language models.Nature biotechnology · 2026Article
- CRISPR-SWITCH (silent mutations with intention to create heterozygotes): a strategy for monoallelic genome editing and generation of aFrontiers in genome editing · 2026Article
- Gene editing for Spinocerebellar ataxia type 3 taking advantage of the human ATXN3L paralog as replacement gene.Gene therapy · 2025Article
- Exploring AAV-Mediated Gene Therapy for Inner Ear Diseases: from Preclinical Success to Clinical Potential.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Article
- Engineering of CRISPR-Cas PAM recognition using deep learning of vast evolutionary data.bioRxiv : the preprint server for biology · 2025Article
- Haplotype editing with CRISPR/Cas9 as a therapeutic approach for dominant-negative missense mutations inbioRxiv : the preprint server for biology · 2024Article
- Peptide Nucleic Acid-Mediated Regulation of CRISPR-Cas9 Specificity.Nucleic acid therapeutics · 2024Article
- Allele-specific CRISPR-Cas9 editing inactivates a single nucleotide variant associated with collagen VI muscular dystrophy.Molecular therapy. Nucleic acids · 2024Article
- Quantifying allele-specific CRISPR editing activity with CRISPECTOR2.0.Nucleic acids research · 2024Article
- Gene therapy for CNS disorders: modalities, delivery and translational challenges.Nature reviews. Neuroscience · 2024Review
- AlPaCas: allele-specific CRISPR gene editing through a protospacer-adjacent-motif (PAM) approach.Nucleic acids research · 2024Article
- Classic lattice corneal dystrophy: a brief review and summary of treatment modalities.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2024Review
- Allele-specific CRISPR/Cas9 editing inactivates a single nucleotide variant associated with collagen VI muscular dystrophy.bioRxiv : the preprint server for biology · 2024Article
- Article
- Massively parallel evaluation and computational prediction of the activities and specificities of 17 small Cas9s.Nature methods · 2023Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CRISPR/Cas9 holds immense potential to treat a range of genetic disorders. Allele-specific gene disruption induced by non-homologous end-joining (NHEJ) DNA repair offers a potential treatment option for autosomal dominant disease. Here, we successfully delivered a plasmid encoding S. pyogenes Cas9 and sgRNA to the corneal epithelium by intrastromal injection and acheived long-term knockdown of a corneal epithelial reporter gene, demonstrating gene disruption via NHEJ in vivo. In addition, we used TGFBI corneal dystrophies as a model of autosomal dominant disease to assess the use of CRISPR/Cas9 in two allele-specific systems, comparing cleavage using a SNP-derived PAM to a guide specific approach. In vitro, cleavage via a SNP-derived PAM was found to confer stringent allele-specific cleavage, while a guide-specific approach lacked the ability to distinguish between the wild-type and mutant alleles. The failings of the guide-specific approach highlights the necessity for meticulous guide design and assessment, as various degrees of allele-specificity are achieved depending on the guide sequence employed. A major concern for the use of CRISPR/Cas9 is its tendency to cleave DNA non-specifically at "off-target" sites. Confirmation that S. pyogenes Cas9 lacks the specificity to discriminate between alleles differing by a single base-pair regardless of the position in the guide is demonstrated.
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