Skeletal muscle-specific expression of human blood coagulation factor IX rescues factor IX deficiency mouse by AAV-mediated gene transfer

Lihui Lai, Li Chen, Jianmin Wang, Hong Zhou, Daru Lu, Qi Wang, Xiaobo Gao, Xinfang Qiu, Jinglun Xue

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

The efficacy of recombinant adeno-associated virus (AAV) vector to deliver and express human blood clotting factor IX (hFIX) gene in skeletal muscle of coagulation factor IX deficiency mouse strain (FactorIX-knockout) is evaluated. The muscle creatine kinase enhancer (MCK) and β-actin promoter (βA) were used to drive the hFIX minigene (hFIXm1), which was flanked by AAV inverted terminal repeats (ITRs). Following intramuscular injection of high titer (2.5 × 1011 vector genomes/mL) of rAAV, increased hFIX expression (256 ng/mL of plasma) was achieved. The time course of hFIX expression demonstrated that the expression level gradually increased over a period of two weeks before anti-hFIX antibodies developed in mouse circulating plasma. Those results provided a promising evidence that rAAV-mediated gene transfer and skeletal muscle-specific expression of hFIX is a feasible strategy for treating patients for hemophilia B.

Original languageEnglish (US)
Pages (from-to)628-634
Number of pages7
JournalScience in China, Series C: Life Sciences
Volume42
Issue number6
StatePublished - Dec 1999

Keywords

  • AAV
  • Direct-muscular gene therapy
  • Factor IX deficiency mouse
  • hFIX

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Environmental Science(all)
  • Agricultural and Biological Sciences(all)

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