ArticleCommunications medicine2023
PAM-flexible Cas9-mediated base editing of a hemophilia B mutation in induced pluripotent stem cells.
Article in Communications medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 24 citations in OpenAlex.
- Gene therapy for hereditary hematological disorders: From clinical breakthroughs to future horizons.Molecular therapy. Nucleic acids · 2026Review
- Base editing for precision therapeutics.Cell genomics · 2026Review
- Article
- Exploring gene editing as a potential therapeutic strategy for hemophilia.Frontiers in bioengineering and biotechnology · 2026Review
- Advancements in CRISPR-basedFrontiers in genome editing · 2026Review
- Appraisal of CRISPR Technology as an Innovative Screening to Therapeutic Toolkit for Genetic Disorders.Molecular biotechnology · 2026Review
- Balancing Promise and Peril: Hemophilia Gene Therapy Insights.IUBMB life · 2026Review
- Review
- Application of Induced Pluripotent Stem Cells (iPSCs) in Hereditary and Viral Diseases of the Liver: Modeling and Treatment.International journal of molecular sciences · 2025Review
- Review
- Off-target interactions in the CRISPR-Cas9 Machinery: mechanisms and outcomes.Biochemistry and biophysics reports · 2025Review
- Induced Pluripotent (iPSC) and Mesenchymal (MSC) Stem Cells for In Vitro Disease Modeling and Regenerative Medicine.International journal of molecular sciences · 2025Review
- Mechanism of Genome Editing Tools and Their Application on Genetic Inheritance Disorders.Global medical genetics · 2024Review
- Glycosylation of recombinant adeno-associated virus serotype 6.Molecular therapy. Methods & clinical development · 2024Article
- Hemophilia Healing with AAV: Navigating the Frontier of Gene Therapy.Current gene therapy · 2024Review
- Genome editing of patient-derived iPSCs identifies a deep intronic variant causing aberrant splicing in hemophilia A.Blood advances · 2023Article
- CRISPR/Cas9 Landscape: Current State and Future Perspectives.International journal of molecular sciences · 2023Review
- Gene Therapy Approaches for the Treatment of Hemophilia B.International journal of molecular sciences · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundBase editing via CRISPR-Cas9 has garnered attention as a method for correcting disease-specific mutations without causing double-strand breaks, thereby avoiding large deletions and translocations in the host chromosome. However, its reliance on the protospacer adjacent motif (PAM) can limit its use. We aimed to restore a disease mutation in a patient with severe hemophilia B using base editing with SpCas9-NG, a modified Cas9 with the board PAM flexibility.
methodsWe generated induced pluripotent stem cells (iPSCs) from a patient with hemophilia B (c.947T>C; I316T) and established HEK293 cells and knock-in mice expressing the patient's F9 cDNA. We transduced the cytidine base editor (C>T), including the nickase version of Cas9 (wild-type SpCas9 or SpCas9-NG), into the HEK293 cells and knock-in mice through plasmid transfection and an adeno-associated virus vector, respectively.
resultsHere we demonstrate the broad PAM flexibility of SpCas9-NG near the mutation site. The base-editing approach using SpCas9-NG but not wild-type SpCas9 successfully converts C to T at the mutation in the iPSCs. Gene-corrected iPSCs differentiate into hepatocyte-like cells in vitro and express substantial levels of F9 mRNA after subrenal capsule transplantation into immunodeficient mice. Additionally, SpCas9-NG-mediated base editing corrects the mutation in both HEK293 cells and knock-in mice, thereby restoring the production of the coagulation factor.
conclusionA base-editing approach utilizing the broad PAM flexibility of SpCas9-NG can provide a solution for the treatment of genetic diseases, including hemophilia B.
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.