ArticleProceedings of the National Academy of Sciences of the United States of America1999
Integrin alphaIIb promoter-targeted expression of gene products in megakaryocytes derived from retrovirus-transduced human hematopoietic cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 56 citations in OpenAlex.
- Recent advances in lentiviral vectors for gene therapy.Science China. Life sciences · 2021Review
- Activated factor X targeted stored in platelets as an effective gene therapy strategy for both hemophilia A and B.Clinical and translational medicine · 2021Article
- Article
- [Current state and prospect in treatment of Glanzmann' s thrombasthenia].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2016Article
- Genetic engineering of platelets to neutralize circulating tumor cells.Journal of controlled release : official journal of the Controlled Release Society · 2016Article
- Review
- Article
- Platelet specific promoters are insufficient to express protease activated receptor 1 (PAR1) transgene in mouse platelets.PloS one · 2014Article
- Glanzmann thrombasthenia: state of the art and future directions.Seminars in thrombosis and hemostasis · 2013Review
- Platelet-targeted gene therapy with human factor VIII establishes haemostasis in dogs with haemophilia A.Nature communications · 2013Article
- High efficiency gene transfer to airways of mice using influenza hemagglutinin pseudotyped lentiviral vectors.The journal of gene medicine · 2013Article
- Correction of murine Bernard-Soulier syndrome by lentivirus-mediated gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Article
- Platelet gene therapy improves hemostatic function for integrin alphaIIbbeta3-deficient dogs.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Review
- Platelets as delivery systems for disease treatments.Advanced drug delivery reviews · 2010Review
- Article
- Factor VIII ectopically targeted to platelets is therapeutic in hemophilia A with high-titer inhibitory antibodies.The Journal of clinical investigation · 2006Article
- Article
- Identification of a gene element essential for leukemia-specific expression of transgenes.Leukemia · 2004Article
- Primary megakaryocytes reveal a role for transcription factor NF-E2 in integrin alpha IIb beta 3 signaling.The Journal of cell biology · 1999Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Megakaryocyte-specific expression of the platelet-adhesion receptor, integrin alphaIIbbeta3, is caused by the presence of regulatory elements of the alphaIIb promoter that direct high-level, selective gene transcription early in megakaryocytopoiesis. To develop methods for targeted expression of transgenes, we transduced human CD34+ peripheral blood cells with a murine leukemia virus (MuLV) vector controlled by the human integrin alphaIIb promoter (nucleotides -889 to +35). A naturally occurring cDNA encoding the Pl(A2) alloantigen form (Pro(33)) of the integrin beta3 subunit was subcloned into this construct (-889Pl(A2)beta3) and transduced into cells that endogenously synthesized Pl(A1)beta3 (Leu(33)) as a marker for detection of provirus-derived beta3. The ability of this vector to target expression of Pl(A2)beta3 to megakaryocytes was first examined in cell lines. Immunoblot analysis with human anti-Pl(A2) alloserum detected synthesis of Pl(A2)beta3 in transduced promegakaryocytic cells; however, Pl(A2)beta3 protein was not detected in transduced epithelial cells. Human hematopoietic CD34+ cells were transduced with -889Pl(A2)beta3 virions and induced to differentiate with megakaryocyte growth and development factor. A hybrid alphaIIbbeta3 complex was formed in progeny megakaryocytes where provirus-derived Pl(A2)beta3 was detected associated with endogenous alphaIIb subunit. Another alphaIIb promoter-driven MuLV vector (-889nlacZ) encoding Escherichia coli beta-galactosidase was used to demonstrate that transgene expression was selectively targeted to the megakaryocyte progeny of transduced CD34+ cells. These studies demonstrate the feasibility of using alphaIIb promoter-driven MuLV vectors for gene transfer of hematopoietic CD34+ cells to target transgene expression in developing megakaryocytes and platelets and indicate potential applications toward human gene therapy for platelet disorders.
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