ArticleMolecular therapy : the journal of the American Society of Gene Therapy2020
Mutation-Independent Allele-Specific Editing by CRISPR-Cas9, a Novel Approach to Treat Autosomal Dominant Disease.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- 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
- CRISPR Base Editing Correction of TGFBI Mutations in Autosomal Dominant Corneal Dystrophies.Investigative ophthalmology & visual science · 2026Article
- Review
- The evolving landscape of NF gene therapy: Hurdles and opportunities.Molecular therapy. Nucleic acids · 2025Review
- Haplotype editing with CRISPR/Cas9 as a therapeutic approach for dominant-negative missense mutations inbioRxiv : the preprint server for biology · 2024Article
- Functional benefit of CRISPR-Cas9-induced allele deletion forMolecular therapy. Nucleic acids · 2024Article
- Allele-specific CRISPR-Cas9 editing inactivates a single nucleotide variant associated with collagen VI muscular dystrophy.Molecular therapy. Nucleic acids · 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
- Epigenetic editing for autosomal dominant neurological disorders.Frontiers in genome editing · 2024Review
- Phenotypic variability to medication management: an update on fragile X syndrome.Human genomics · 2023Review
- A highly specific CRISPR-Cas12j nuclease enables allele-specific genome editing.Science advances · 2023Article
- CRISPR/Cas therapeutic strategies for autosomal dominant disorders.The Journal of clinical investigation · 2022Review
- Recent advances in gene therapy for neurodevelopmental disorders with epilepsy.Journal of neurochemistry · 2021Review
- Prime Editing for Inherited Retinal Diseases.Frontiers in genome editing · 2021Review
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CRISPR-Cas9 provides a tool to treat autosomal dominant disease by non-homologous end joining (NHEJ) gene disruption of the mutant allele. In order to discriminate between wild-type and mutant alleles, Streptococcus pyogenes Cas9 (SpCas9) must be able to detect a single nucleotide change. Allele-specific editing can be achieved by using either a guide-specific approach, in which the missense mutation is found within the guide sequence, or a protospacer-adjacent motif (PAM)-specific approach, in which the missense mutation generates a novel PAM. While both approaches have been shown to offer allele specificity in certain contexts, in cases where numerous missense mutations are associated with a particular disease, such as TGFBI (transforming growth factor β-induced) corneal dystrophies, it is neither possible nor realistic to target each mutation individually. In this study, we demonstrate allele-specific CRISPR gene editing independent of the disease-causing mutation that is capable of achieving complete allele discrimination, and we propose it as a targeting approach for autosomal dominant disease. Our approach utilizes natural variants in the target region that contain a PAM on one allele that lies in cis with the causative mutation, removing the constraints of a mutation-dependent approach. Our innovative patient-specific guide design approach takes into account the patient's individual genetic make-up, allowing on- and off-target activity to be assessed in a personalized manner.
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