ArticleMolecular therapy : the journal of the American Society of Gene Therapy2007
The enhancing effects of the light chain on heavy chain secretion in split delivery of factor VIII gene.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed, 44 citations in OpenAlex.
- Article
- Systemic delivery of full-length dystrophin in Duchenne muscular dystrophy mice.Nature communications · 2024Article
- AAV vectors: The Rubik's cube of human gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- Liver gene therapy with intein-mediated F8 trans-splicing corrects mouse haemophilia A.EMBO molecular medicine · 2022Article
- Minimal Essential Human Factor VIII Alterations Enhance Secretion and Gene Therapy Efficiency.Molecular therapy. Methods & clinical development · 2020Article
- Article
- Evaluation of the activity levels of rat FVIII and human FVIII delivered by adeno-associated viral vectors both in vitro and in vivo.Blood cells, molecules & diseases · 2018Article
- Evaluation of the biological differences of canine and human factor VIII in gene delivery: implications in human hemophilia treatment.Gene therapy · 2016Article
- Gene therapy for hemophilia.Frontiers in bioscience (Landmark edition) · 2015Review
- Efficient production of dual recombinant adeno-associated viral vectors for factor VIII delivery.Human gene therapy methods · 2014Article
- Article
- Light chain of factor VIII is sufficient for accelerating cleavage of von Willebrand factor by ADAMTS13 metalloprotease.The Journal of biological chemistry · 2012Article
- Liver-Directed Adeno-Associated Viral Gene Therapy for Hemophilia.Journal of genetic syndromes & gene therapy · 2012Article
- Engineering Factor Viii for Hemophilia Gene Therapy.Journal of genetic syndromes & gene therapy · 2011Article
- Advances in Gene Delivery Systems.Pharmaceutical medicine · 2011Article
- Proteasome inhibitors enhance gene delivery by AAV virus vectors expressing large genomes in hemophilia mouse and dog models: a strategy for broad clinical application.Molecular therapy : the journal of the American Society of Gene Therapy · 2010Article
- Characterization of genome integrity for oversized recombinant AAV vector.Molecular therapy : the journal of the American Society of Gene Therapy · 2010Article
- Advancements in gene transfer-based therapy for hemophilia A.Expert review of hematology · 2009Article
- Enhanced factor VIII heavy chain for gene therapy of hemophilia A.Molecular therapy : the journal of the American Society of Gene Therapy · 2009Article
- Protein replacement therapy and gene transfer in canine models of hemophilia A, hemophilia B, von willebrand disease, and factor VII deficiency.ILAR journal · 2009Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 7 institutions in 3 countries.
Funding
Abstract
Coagulation factor VIII (FVIII) is secreted as a heterodimer consisting of a heavy chain (HC) and a light chain (LC), which can be expressed independently and reassociate with recovery of biological activity. Because of the size limitation of adeno-associated virus (AAV) vectors, a strategy for delivering the HC and LC separately has been developed. However, the FVIII HC is secreted 10-100-fold less efficiently than the LC. In this study, we demonstrated that the F309S mutation and enhanced B-domain glycosylations alone are not sufficient to improve FVIII HC secretion, which suggested a role of the FVIII LC in regulating HC secretion. To characterize this role of the FVIII LC, we compared FVIII HC secretion with and without the LC via post-translational protein trans-splicing. As demonstrated in vitro, ligation of the LC to the HC significantly increased HC secretion. Such HC secretion increases were also confirmed in vivo by hydrodynamic injection of FVIII intein plasmids into hemophilia A mice. Moreover, similar enhancement of HC secretion can also be observed when the LC is supplied in trans, which is probably due to the spontaneous association of the HC and the LC in the secretion pathway. In sum, enhancing the secretion of the FVIII HC polypeptide may require the proper association of the FVIII LC polypeptide in cis or in trans. These results may be helpful in designing new strategies to improve FVIII gene delivery.
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.