Inclusion Criteria:

• Males ≥ 18 years of age with established severe HB (FIX:C<1u/dl) resulting from a missense mutation in the hFIX gene which has not been associated with an inhibitor in the database(http://www.kcl.ac.uk/ip/petergreen/haemBdatabase.html)with detectable FIX in serum.Individuals with a stop codon mutation, a promoter mutation, a small insertion or deletion causing a frame shift, a small in frame insertion or deletion or a splice junction mutation may be enrolled if their mutation has not been associated with an inhibitor,
• Treated/exposed to FIX concentrates for at least 10 years,
• A minimum of an average of 3 bleeding episodes per year requiring FIX infusions or prophylactic FIX infusions because of frequent prior bleeding episodes
• Able to give informed consent and comply with requirements of the trial
• Currently free of inhibitor and have no history of inhibitors to FIX protein
• A negative family history for the development of an inhibitor,
• Willing to practice a reliable barrier method of contraception until 3 sequential samples are negative for vector genomes using our PCR assay.

Exclusion Criteria:

• Evidence of active infection with Hepatitis B or C virus as reflected by HBsAg or HCV RNA positivity, respectively. To be considered negative for active infection, two negative assays at a minimum of a six month interval are required
• Exposure to Hepatitis B or C who are currently on antiviral therapy
• Serological evidence of HIV or HTLV infection because of the potential need for immunosuppression
• Significant liver dysfunction as defined by an abnormal ALT (alanine transaminase), bilirubin, alkaline phosphatase or INR. Potential participants who have had a liver biopsy in the past 3 years will be excluded if they have significant fibrosis of 3 or 4 as rated on a scale of 0-4.
• Coronary artery disease as a co-morbid condition
• Platelet count of <150 x 10 to the power of 9/l
• Creatinine ≥ 1.5 mg/dl
• Hypertension with systolic BP ≥ 130 mmHg or diastolic BP ≥ 90 mmHg, persistently or on treatment for hypertension
• History of active tuberculosis, fungal disease or other chronic infection
• History of chronic disease that would adversely affect performance
• Detectable antibodies reactive with AAV8
• Subjects who must remain on, or choose to remain on, prophylactic FIX concentrates
• Subjects who are unwilling to provide the required semen samples
• Poor performance status (WHO performance status score >1) or
• Received a gene transfer agent in the previous 6 months