Frontiers of Medicine

, Volume 10, Issue 2, pp 212–218 | Cite as

Gene therapy for hemophilia B mice with scAAV8-LP1-hFIX

  • Wei Lu
  • Qingzhang Zhou
  • Hao Yang
  • Hao Wang
  • Yexing Gu
  • Qi Shen
  • Jinglun Xue
  • Xiaoyan DongEmail author
  • Jinzhong ChenEmail author
Research Article


Hemophilia B is a hemorrhagic disease caused by the deficiency of clotting factor IX (FIX). Gene therapy might be the ultimate strategy for the disease. However, two main problems that should be solved in gene therapy for hemophilia B are immunity and safety. Self-complementary adeno-associated virus serotype 8 (scAAV8), a non-human primate AAV featuring low immunogenicity and high transfection efficiency in liver cells, might be a potential vector for hemophilia B gene therapy. A strong liver-specific promoter-1 (LP1) was inserted and mutant human FIX Arg338Ala was introduced into plasmid scAAV8-LP1 to develop an optimized AAV8 vector that expresses human clotting factor FIX (hFIX). The efficiency of scAAV8-LP1-hFIX administered through normal systemic injection or hydrodynamic injection was compared. A high expression was achieved using hydrodynamic injection, and the peak hFIX expression levels in the 5 × 1011 and 1 × 1011 virus genome (vg) cohorts were 31.94% and 25.02% of normal level, respectively, at 60 days post-injection. From the perspective of long-term (200 days) expression, both injection methods presented promising results with the concentration value maintained above 4% of normal plasma. The results were further verified by enzyme-linked immunosorbent assay and activated partial thromboplastin time. Our study provides a potential gene therapy method for hemophilia B.


hemophilia B AAV8 hFIX gene therapy 


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Copyright information

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Wei Lu
    • 1
  • Qingzhang Zhou
    • 2
    • 3
  • Hao Yang
    • 1
  • Hao Wang
    • 1
  • Yexing Gu
    • 1
  • Qi Shen
    • 1
  • Jinglun Xue
    • 1
  • Xiaoyan Dong
    • 2
    Email author
  • Jinzhong Chen
    • 1
    Email author
  1. 1.State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life SciencesFudan UniversityShanghaiChina
  2. 2.Beijing Five Plus Molecular Medicine InstituteBeijingChina
  3. 3.College of Life SciencesJilin UniversityChangchunChina

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