Therapeutic levels of functional human factor X in rats after retroviral-mediated hepatic gene therapy

Mai Thao Le, Torayuki Okuyama, Shi Rong Cai, Susan C. Kennedy, William M. Bowling, M. Wayne Flye, Katherine Parker Ponder

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


Factor X deficiency results in a rare but serious bleeding disorder that might be treated by expressing a normal factor X gene in patients. We generated an amphotropic retroviral vector with the human FX cDNA and delivered it to rat hepatocytes in vivo during liver regeneration. The human α1-antitrypsin promoter was chosen to direct expression because it was the most efficient of several tested in yielding expression of α1-antitrypsin protein from a retroviral vector in hepatocytes in vivo. We achieved expression of factor X in four rats at levels sufficient to maintain hemostasis in humans (10% to 43% of normal). The factor X was determined to be functional by using a chromogenic substrate assay after immunoprecipitation with human specific antibodies. Expression of factor X remained stable for more than 10 months in two rats. It is likely that expression will be maintained for the life of the animals, because retroviral vectors integrate into the chromosome and hepatocytes are long-lived. The high and stable levels of expression achieved using this liver-specific promoter overcomes one of the two major obstacles to successful human gene therapy for hemophilia.

Original languageEnglish
Pages (from-to)1254-1259
Number of pages6
Issue number4
StatePublished - Feb 15 1997


Dive into the research topics of 'Therapeutic levels of functional human factor X in rats after retroviral-mediated hepatic gene therapy'. Together they form a unique fingerprint.

Cite this