Skip to main content

Persistent expression of factor VIII in vivo following nonprimate lentiviral gene transfer

Publication ,  Journal Article
Kang, Y; Xie, L; Tran, DT; Stein, CS; Hickey, M; Davidson, BL; McCray, PB
Published in: Blood
September 1, 2005

Hemophilia A is a clinically important coagulation disorder caused by the lack or abnormality of plasma coagulation factor VIII (FVIII). Gene transfer of the FVIII cDNA to hepatocytes using lentiviral vectors is a potential therapeutic approach. We investigated the efficacy of feline immunodeficiency virus (FIV)–based vectors in targeting hepatocytes and correcting FVIII deficiency in a hemophilia A mouse model. Several viral envelope glycoproteins were screened for efficient FIV vector pseudotyping and hepatocyte transduction. The GP64 glycoprotein from baculovirus Autographa californica multinuclear polyhedrosis virus pseudo-typed FIV efficiently and showed excellent hepatocyte tropism. The GP64-pseudotyped vector was stable in the presence of human or mouse complement. Inclusion of a hybrid liver-specific promoter (murine albumin enhancer/human α1-antitrypsin promoter) further enhanced transgene expression in hepatocytes. We generated a GP64-pseudotyped FIV vector encoding the B domain–deleted human FVIII coding region driven by the liver-specific promoter, with 2 beneficial point mutations in the A1 domain. Intravenous vector administration conferred sustained FVIII expression in hemophilia A mice for several months without the generation of anti–human FVIII antibodies and resulted in partial phenotypic correction. These findings demonstrate the utility of GP64-pseudotyped FIV lentiviral vectors for targeting hepatocytes to correct disorders associated with deficiencies of secreted proteins.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Blood

DOI

EISSN

1528-0020

ISSN

0006-4971

Publication Date

September 1, 2005

Volume

106

Issue

5

Start / End Page

1552 / 1558

Publisher

American Society of Hematology

Related Subject Headings

  • Immunology
  • 3213 Paediatrics
  • 3201 Cardiovascular medicine and haematology
  • 3101 Biochemistry and cell biology
  • 1114 Paediatrics and Reproductive Medicine
  • 1103 Clinical Sciences
  • 1102 Cardiorespiratory Medicine and Haematology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kang, Y., Xie, L., Tran, D. T., Stein, C. S., Hickey, M., Davidson, B. L., & McCray, P. B. (2005). Persistent expression of factor VIII in vivo following nonprimate lentiviral gene transfer. Blood, 106(5), 1552–1558. https://doi.org/10.1182/blood-2004-11-4358
Kang, Yubin, Litao Xie, Diane Thi Tran, Colleen S. Stein, Melissa Hickey, Beverly L. Davidson, and Paul B. McCray. “Persistent expression of factor VIII in vivo following nonprimate lentiviral gene transfer.” Blood 106, no. 5 (September 1, 2005): 1552–58. https://doi.org/10.1182/blood-2004-11-4358.
Kang Y, Xie L, Tran DT, Stein CS, Hickey M, Davidson BL, et al. Persistent expression of factor VIII in vivo following nonprimate lentiviral gene transfer. Blood. 2005 Sep 1;106(5):1552–8.
Kang, Yubin, et al. “Persistent expression of factor VIII in vivo following nonprimate lentiviral gene transfer.” Blood, vol. 106, no. 5, American Society of Hematology, Sept. 2005, pp. 1552–58. Crossref, doi:10.1182/blood-2004-11-4358.
Kang Y, Xie L, Tran DT, Stein CS, Hickey M, Davidson BL, McCray PB. Persistent expression of factor VIII in vivo following nonprimate lentiviral gene transfer. Blood. American Society of Hematology; 2005 Sep 1;106(5):1552–1558.

Published In

Blood

DOI

EISSN

1528-0020

ISSN

0006-4971

Publication Date

September 1, 2005

Volume

106

Issue

5

Start / End Page

1552 / 1558

Publisher

American Society of Hematology

Related Subject Headings

  • Immunology
  • 3213 Paediatrics
  • 3201 Cardiovascular medicine and haematology
  • 3101 Biochemistry and cell biology
  • 1114 Paediatrics and Reproductive Medicine
  • 1103 Clinical Sciences
  • 1102 Cardiorespiratory Medicine and Haematology