ArticleGene therapy2013
Zinc-finger nuclease-mediated gene correction using single AAV vector transduction and enhancement by Food and Drug Administration-approved drugs.
Article in Gene therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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
42 citing papers in PubMed, 84 citations in OpenAlex.
- Assessing the biopotency of the rAAV9 vector In Vitro.PloS one · 2026Article
- Prospects of viral vector-mediated delivery of sequences encoding anti-HBV designer endonucleases.Gene therapy · 2025Review
- Methods of crop improvement and applications towards fortifying food security.Frontiers in genome editing · 2023Review
- Article
- Use of Genome Editing Techniques to Produce Transgenic Farm Animals.Advances in experimental medicine and biology · 2022Review
- Targeted Gene Insertion for Functional CFTR Restoration in Airway Epithelium.Frontiers in genome editing · 2022Article
- CRISPR-Cas9: A method for establishing rat models of drug metabolism and pharmacokinetics.Acta pharmaceutica Sinica. B · 2021Review
- CRISPR/Cas: a Nobel Prize award-winning precise genome editing technology for gene therapy and crop improvement.Journal of Zhejiang University. Science. B · 2021Review
- Correction of Airway Stem Cells: Genome Editing Approaches for the Treatment of Cystic Fibrosis.Human gene therapy · 2020Review
- Precision gene editing technology and applications in nephrology.Nature reviews. Nephrology · 2018Review
- Genome editing for the treatment of tumorigenic viral infections and virus-related carcinomas.Frontiers of medicine · 2018Review
- Use of gene-editing technology to introduce targeted modifications in pigs.Journal of animal science and biotechnology · 2018Review
- A history of genome editing in mammals.Mammalian genome : official journal of the International Mammalian Genome Society · 2017Review
- Optogenetic Modulation of Intracellular Signalling and Transcription: Focus on Neuronal Plasticity.Journal of experimental neuroscience · 2017Review
- Emerging therapies for mitochondrial disorders.Brain : a journal of neurology · 2016Review
- In Vivo Delivery Systems for Therapeutic Genome Editing.International journal of molecular sciences · 2016Review
- Improved methods of AAV-mediated gene targeting for human cell lines using ribosome-skipping 2A peptide.Nucleic acids research · 2016Article
- Engineered Viruses as Genome Editing Devices.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Review
- Genome Engineering Using Adeno-associated Virus: Basic and Clinical Research Applications.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Review
- Genome Editing in Human Pluripotent Stem Cells: Approaches, Pitfalls, and Solutions.Cell stem cell · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
An emerging strategy for the treatment of monogenic diseases uses genetic engineering to precisely correct the mutation(s) at the genome level. Recent advancements in this technology have demonstrated therapeutic levels of gene correction using a zinc-finger nuclease (ZFN)-induced DNA double-strand break in conjunction with an exogenous DNA donor substrate. This strategy requires efficient nucleic acid delivery and among viral vectors, recombinant adeno-associated virus (rAAV) has demonstrated clinical success without pathology. However, a major limitation of rAAV is the small DNA packaging capacity and to date, the use of rAAV for ZFN gene delivery has yet to be reported. Theoretically, an ideal situation is to deliver both ZFNs and the repair substrate in a single vector to avoid inefficient gene targeting and unwanted mutagenesis, both complications of a rAAV co-transduction strategy. Therefore, a rAAV format was generated in which a single polypeptide encodes the ZFN monomers connected by a ribosome skipping 2A peptide and furin cleavage sequence. On the basis of this arrangement, a DNA repair substrate of 750 nucleotides was also included in this vector. Efficient polypeptide processing to discrete ZFNs is demonstrated, as well as the ability of this single vector format to stimulate efficient gene targeting in a human cell line and mouse model derived fibroblasts. Additionally, we increased rAAV-mediated gene correction up to sixfold using a combination of Food and Drug Administration-approved drugs, which act at the level of AAV vector transduction. Collectively, these experiments demonstrate the ability to deliver ZFNs and a repair substrate by a single AAV vector and offer insights for the optimization of rAAV-mediated gene correction using drug therapy.
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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.