Therapeutic levels of human factor VIII and IX using HIV-1-based lentiviral vectors in mouse liver

Frank Park, Kazuo Ohashi, Mark A. Kay

Research output: Contribution to journalArticle

136 Citations (Scopus)

Abstract

Lentiviral vectors have the potential to play an important role in hemophilia gene therapy. The present study used human immunodeficiency virus (HIV)-based lentiviral vectors containing an EF1α enhancer/promoter driving human factors VIII (hFVIII) or IX (hFIX) complementary DNA expression for portal vein injection into C571BI/6 mice. Increasing doses of hFIX-expressing lentivirus resulted in a dose-dependent, sustained increase in serum hFIX levels up to approximately 50-60 ng/mL. Partial hepatectomy resulted in a 4- to 6-fold increase (P < 0.005) in serum hFIX of up to 350 ng/mL compared with the nonhepatectomized counterparts. The expression of plasma hFVIII reached 30 ng/mL (15% of normal) but was transient as the plasma levels fell concomitant with the formation of anti-hFVIII antibodies. However, hFVIII levels were persistent in immunodefi- hepatocellular proliferation. (C) 2000 by The American Society of Hematology.

Original languageEnglish (US)
Pages (from-to)1173-1176
Number of pages4
JournalBlood
Volume96
Issue number3
StatePublished - Aug 1 2000
Externally publishedYes

Fingerprint

Factor IX
Viruses
Liver
HIV-1
Plasma (human)
Gene therapy
Lentivirus
Hemophilia A
Hepatectomy
Therapeutics
Portal Vein
Serum
Genetic Therapy
Complementary DNA
HIV
Plasmas
Injections
human F8 protein
Antibodies

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Therapeutic levels of human factor VIII and IX using HIV-1-based lentiviral vectors in mouse liver. / Park, Frank; Ohashi, Kazuo; Kay, Mark A.

In: Blood, Vol. 96, No. 3, 01.08.2000, p. 1173-1176.

Research output: Contribution to journalArticle

Park, Frank ; Ohashi, Kazuo ; Kay, Mark A. / Therapeutic levels of human factor VIII and IX using HIV-1-based lentiviral vectors in mouse liver. In: Blood. 2000 ; Vol. 96, No. 3. pp. 1173-1176.
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