ArticleHuman gene therapy2012
Long-term expression of human coagulation factor VIII in a tolerant mouse model using the φC31 integrase system.
Article in Human gene therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 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
11 citing papers in PubMed, 22 citations in OpenAlex.
- Transformative approaches in hemophilia management: from traditional therapies to prenatal stem cell treatment.Frontiers in bioengineering and biotechnology · 2025Review
- Global mapping of binding sites for phic31 integrase in transgenic maden-darby bovine kidney cells using ChIP-seq.Hereditas · 2019Article
- Genome Integration and Excision by a New Streptomyces Bacteriophage, ϕJoe.Applied and environmental microbiology · 2017Article
- Liver-targeted gene therapy: Approaches and challenges.Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society · 2015Review
- Neuroprotective therapies in glaucoma: II. Genetic nanotechnology tools.Frontiers in neuroscience · 2015Review
- New applications for phage integrases.Journal of molecular biology · 2014Review
- Intragenic integration in DLC1 sustains factor VIII expression in primary human cells without insertional oncogenicity.Gene therapy · 2014Article
- piggyBac-mediated phenotypic correction of factor VIII deficiency.Molecular therapy. Methods & clinical development · 2014Article
- Delivery of full-length factor VIII using a piggyBac transposon vector to correct a mouse model of hemophilia A.PloS one · 2014Article
- Hybrid lentivirus-phiC31-int-NLS vector allows site-specific recombination in murine and human cells but induces DNA damage.PloS one · 2014Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
We generated a mouse model for hemophilia A that combines a homozygous knockout for murine factor VIII (FVIII) and a homozygous addition of a mutant human FVIII (hFVIII). The resulting mouse, having no detectable FVIII protein or activity and tolerant to hFVIII, is useful for evaluating FVIII gene-therapy protocols. This model was used to develop an effective gene-therapy strategy using the φC31 integrase to mediate permanent genomic integration of an hFVIII cDNA deleted for the B-domain. Various plasmids encoding φC31 integrase and hFVIII were delivered to the livers of these mice by using hydrodynamic tail-vein injection. Long-term expression of therapeutic levels of hFVIII was observed over a 6-month time course when an intron was included in the hFVIII expression cassette and wild-type φC31 integrase was used. A second dose of the hFVIII and integrase plasmids resulted in higher long-term hFVIII levels, indicating that incremental doses were beneficial and that a second dose of φC31 integrase was tolerated. We observed a significant decrease in the bleeding time after a tail-clip challenge in mice treated with plasmids expressing hFVIII and φC31 integrase. Genomic integration of the hFVIII expression plasmid was demonstrated by junction PCR at a known hotspot for integration in mouse liver. The φC31 integrase system provided a nonviral method to achieve long-term FVIII gene therapy in a relevant mouse model of hemophilia A.
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.