title: Efficient delivery of human clotting factor IX after injection of lentiviral vectors in utero.
abstract: OBJECTIVE
  To explore gene transfer feasibility for human clotting factor IX (hFIX) mediated by recombinant lentivirus in utero.
  
  
  METHODS
  ICR mice fetus at 17-19 d gestation were received lentiviral vectors carrying hFIX cDNA under the control of liver specific promoter by intrahepatic injection. The expression and distribution of hFIX cDNA and possible immune responses against the hFIX were assessed by ELISA, PCR, RT-PCR, and immunohistochemistry, respectively.
  
  
  RESULTS
  The serum hFIX protein were detected at different time points in all newborn mice, the highest level of hFIX was 50 microg/L and lasted for more than 30 d. Anti-hFIX antibody was not detected. hFIX cDNA was detected in liver, spleen, and heart. The expression of hFIX cDNA was only detected in liver. Besides, no germ line transmission was found at DNA and RNA levels, and no side effect associated with gene transfer was detected.
  
  
  CONCLUSIONS
  The efficient delivery of hFIX can be achieved by prenatal gene transfer. It thus shows the feasibility of gene therapy for hemophilia in utero.
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Chen
authors.forename: Huan-Zhang
authors.initials: HZ
authors.lastname: Zhu
authors.forename: Ju-Li
authors.initials: JL
authors.lastname: Gong
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Jing-Lun
authors.initials: JL
authors.lastname: Xue
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018076:DNA, Complementary / Q000032:analysis; D005164:Factor IX / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D013154:Spleen / Q000378:metabolism; D019076:Transgenes / Q000235:genetics; D014599:Uterus / Q000378:metabolism
chemical_list: D018076:DNA, Complementary; D011994:Recombinant Proteins; D005164:Factor IX