ArticleMolecular therapy : the journal of the American Society of Gene Therapy2018
Efficient In Vivo Liver-Directed Gene Editing Using CRISPR/Cas9.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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
33 citing papers in PubMed, 63 citations in OpenAlex.
- Ligase-mediated programmable genomic integration (L-PGI).Nature communications · 2025Article
- Identification of a robust promoter in mouse and human hepatocytes by in vivo biopanning of a barcoded AAV library.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- The combination of rAAV pseudo-lipid nanoparticle and triamcinolone acetonide enables multi-administration to liver.Molecular therapy. Methods & clinical development · 2025Article
- Comprehensive analysis of off-target and on-target effects resulting from liver-directed CRISPR-Cas9-mediated gene targeting with AAV vectors.Molecular therapy. Methods & clinical development · 2024Article
- One-stepFrontiers in cell and developmental biology · 2024Article
- Liver lobe-specific hydrodynamic gene delivery to baboons: A preclinical trial for hemophilia gene therapy.Molecular therapy. Nucleic acids · 2023Article
- A Review of CRISPR Tools for Treating Usher Syndrome: Applicability, Safety, Efficiency, and In Vivo Delivery.International journal of molecular sciences · 2023Review
- An IL-6/STAT3/MR/FGF21 axis mediates heart-liver cross-talk after myocardial infarction.Science advances · 2023Article
- Current approaches and potential challenges in the delivery of gene editing cargos into hematopoietic stem and progenitor cells.Frontiers in genome editing · 2023Review
- CRISPR/dCas9 for hepatic fibrosis therapy: implications and challenges.Molecular biology reports · 2022Review
- Current updates of CRISPR/Cas9-mediated genome editing and targeting within tumor cells: an innovative strategy of cancer management.Cancer communications (London, England) · 2022Review
- Self-cleaving guide RNAs enable pharmacological selection of precise gene editing events in vivo.Nature communications · 2022Article
- CRISPR-mediated rapid generation of neural cell-specific knockout mice facilitates research in neurophysiology and pathology.Molecular therapy. Methods & clinical development · 2021Article
- CRISPR/Cas-Dependent and Nuclease-FreeHuman gene therapy · 2021Review
- Approach for in vivo delivery of CRISPR/Cas system: a recent update and future prospect.Cellular and molecular life sciences : CMLS · 2021Review
- CRISPR-Cas9: A Preclinical and Clinical Perspective for the Treatment of Human Diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- Human iPSCs and Genome Editing Technologies for Precision Cardiovascular Tissue Engineering.Frontiers in cell and developmental biology · 2021Review
- CRISPR/Cas9-MediatedFrontiers in cell and developmental biology · 2021Article
- CRISPR/Cas9: A powerful genome editing technique for the treatment of cancer cells with present challenges and future directions.Life sciences · 2020Review
- CRISPR/Cas9 from bench to bedside: what clinicians need to know before application?Military Medical Research · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In vivo tissue-specific genome editing at the desired loci is still a challenge. Here, we report that AAV9-delivery of truncated guide RNAs (gRNAs) and Cas9 under the control of a computationally designed hepatocyte-specific promoter lead to liver-specific and sequence-specific targeting in the mouse factor IX (F9) gene. The efficiency of in vivo targeting was assessed by T7E1 assays, site-specific Sanger sequencing, and deep sequencing of on-target and putative off-target sites. Though AAV9 transduction was apparent in multiple tissues and organs, Cas9 expression was restricted mainly to the liver, with only minimal or no expression in other non-hepatic tissues. Consequently, the insertions and deletion (indel) frequency was robust in the liver (up to 50%) in the desired target loci of the F9 gene, with no evidence of targeting in other organs or other putative off-target sites. This resulted in a substantial loss of FIX activity and the emergence of a bleeding phenotype, consistent with hemophilia B. The in vivo efficacy of the truncated gRNA was as high as that of full-length gRNA. Cas9 expression was transient in neonates, representing an attractive "hit-and-run" paradigm. Our findings have potentially broad implications for somatic gene targeting in the liver using the CRISPR/Cas9 platform.
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.