title: A comparative study of hFIX expression mediated by rAAV8 and rAAV1 administrated intramuscularly.
abstract: BACKGROUND
  Recombinant AAV serotype 8 (rAAV8) vector is relatively new for gene therapy. In this study, the hFIX expression mediated by rAAV8 injected intramuscularly was compared with that by rAAV1.
  
  
  METHODS
  rAAV8-hFIX or rAAV1-hFIX viruses were injected intramuscularly into two hind limbs of mice at doses of 5x10(10) gc and 2.5x10(12) gc (genome copy). The hFIX expression in the mouse plasma was detected by ELISA, APTT and Western blotting. The virus distribution was analyzed by immunohistochemical assay.
  
  
  RESULTS
  When the mice were infected with 5x10(10) gc virus, high levels of hFIX in the plasma of five rAAV8-hFIX virus-infected mice were detected 2 weeks after injection. A hFIX peak above 5000 ng/mL appeared between 2 and 6 weeks after injection. Relatively low levels of hFIX were detected in the plasma of rAAV1-hFIX virus-infected mice 2 weeks after injection. An hFIX peak above 3000 ng/mL appeared between 4 and 10 weeks after injection. However, much lower levels of hFIX were detected in mice infected with higher dose of rAAV8 virus. The hFIX in the mouse plasma was active biologically. The viruses were distributed mainly in the muscles of hind limbs.
  
  
  CONCLUSIONS
  Gene expression mediated by rAAV8 was sooner and stronger than that by rAAV1 after intramuscular administration. Inhibition might have been triggered markedly by rAAV8 at high doses.
authors: College of Life Science and Technology, Jinan University, Guangzhou, China. caozuowu@yahoo.com.cn
authors: Z
authors: Z
authors: Cao
authors: P
authors: P
authors: Zheng
authors: Y
authors: Y
authors: Lin
mesh_terms: D000818:Animals; D001777:Blood Coagulation; D015153:Blotting, Western; D000229:Dependovirus / Q000235:genetics* / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005164:Factor IX / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007273:Injections, Intramuscular; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D010322:Parvoviridae Infections; D011994:Recombinant Proteins / Q000097:blood
chemical_list: D011994:Recombinant Proteins; D005164:Factor IX