Lentivirus-mediated platelet-derived factor VIII gene therapy in murine haemophilia A.

Lentivirus-mediated platelet-derived factor VIII gene therapy in murine haemophilia A. Research Abstract Details 

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Lentivirus-mediated platelet-derived factor VIII gene therapy in murine haemophilia A. Abstract Text:

Q Shi,D A Wilcox,S A Fahs,J Fang,B D Johnson,L M DU,D Desai,R R Montgomery,

BACKGROUND: Previous studies from our laboratory have demonstrated that lineage-targeted synthesis of factor VIII (FVIII) under the direction of the platelet-specific integrin alphaIIb gene promoter (2bF8) can correct the murine haemophilia A phenotype even in the presence of high titer inhibitory antibodies in a transgenic mouse model. OBJECTIVE: In this study, we assessed the efficacy of using a genetic therapy approach to correct haemophilia A in FVIII-deficient (FVIII(null)) mice by transplantation of bone marrow (BM) transduced with a lentivirus (LV)-based gene transfer cassette encoding 2bF8. RESULTS: Functional FVIII activity (FVIII:C) was detected in platelet lysates from treated mice and the levels were similar to 2bF8 heterozygous transgenic mice. Mice transplanted with 2bF8 LV-transduced BM survived tail clipping and we did not detected inhibitory or non-inhibitory FVIII antibodies over the period of this study (11 months). Furthermore, BM transferred from the primary transplant recipients into FVIII(null) secondary recipients demonstrated sustained platelet-FVIII expression leading to correction of the haemophilia A phenotype showing that gene transfer occurred within long-term repopulating haematopoietic stem cells. CONCLUSIONS: These results demonstrate that ectopic expression of FVIII in platelets by lentivirus-mediated bone marrow transduction/transplantation may be a promising strategy for gene therapy of haemophilia A in humans.

Lentivirus-mediated platelet-derived factor VIII gene therapy in murine haemophilia A. Publishing Authors By Initials

Q Shi,DA Wilcox,SA Fahs,J Fang,BD Johnson,LM DU,D Desai,RR Montgomery,

For similar investigative techniques: genetic techniques: gene transfer techniques: transduction, genetic research abstracts see: investigative techniques: genetic techniques: gene transfer techniques: transduction, genetic research

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Lentivirus-mediated platelet-derived factor VIII gene therapy in murine haemophilia A. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of thrombosis and haemostasis : JTH

VOLUME: 5

Page Numbers: 352-61

Journal Abbreviation: J. Thromb. Haemost.

ISSN: 1538-7933

DAY: 3

MONTH: Feb

YEAR: 2007

Lentivirus-mediated platelet-derived factor VIII gene therapy in murine haemophilia A. Information

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LANGUAGE: eng

NlmUniqueID: 101170508

Lentivirus-mediated platelet-derived factor VIII gene therapy in murine haemophilia A. Keywords Mesh Terms:

KEYWORDS: Transduction, Genetic

MESH TERMS: genetics

Chemical & Substance for Abstract: Lentivirus-mediated platelet-derived factor VIII gene therapy in murine haemophilia A. Information

Substance Name: Factor VIII

Registry Number: 9001-27-8

Grant and Affiliation Information for Lentivirus-mediated platelet-derived factor VIII gene therapy in murine haemophilia A.

AFFILIATION: Department of Pediatrics, Medical College of Wisconsin Milwaukee, WI 53226, USA. qizhen.shi@bcw.edu

Country: England

AGENCY: United States NHLBI

GRANT: HL-44612

ACRONYM: HL

MEDLINETA: J Thromb Haemost

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