Delivery of factor VIII gene into skeletal muscle cells using lentiviral vector

• Published in: Yonsei medical journal Vol. 51; no. 1; pp. 52 - 57
• Main Authors: Jeon, Hyun Jeong, Oh, Tae Keun, Kim, Oak Hee, Kim, Seung Taik
• Format: Journal Article
• Language: English
• Published: Korea (South) Yonsei University College of Medicine 01.01.2010; 연세대학교의과대학
• Subjects: Animals; Antibodies - blood; Antibodies - immunology; beta-Galactosidase; Factor VIII - genetics; Factor VIII - immunology; Factor VIII - metabolism; Genetic Therapy; Genetic Vectors - genetics; HeLa Cells; Hemophilia A - therapy; Humans; Lentivirus - genetics; Male; Muscle, Skeletal - metabolism; Original; Rats; Rats, Sprague-Dawley; Transduction, Genetic; 의학일반; human coagulation factor VIII; hemophilia A; Gene therapy; lentiviral vector
• ISSN: 0513-5796; 1976-2437
• DOI: 10.3349/ymj.2010.51.1.52

This study was designed to investigate whether transduction of lentiviral vectors (LV) carrying human coagulation factor VIII (hFVIII) cDNA into skeletal muscle could increase circulating hFVIII concentrations. A LV containing bacterial LacZ gene as a control or human FVIII gene was intramuscularly administered into the thigh muscle of 5 weeks old Sparague-Dawley rats. The plasma human FVIII concentration and neutralizing anti-FVIII antibodies were measured for up to 12 weeks in these experimental animals. The plasma human FVIII levels in the rats injected with LV carrying FVIII cDNA peaked at post-injection 1st week (5.19 +/- 0.14 ng/mL vs. 0.21 +/- 0.05 ng/mL in control rats , p < 0.05). Elevated hFVIII concentrations were maintained for 4 weeks (2.52 +/- 0.83 ng/mL vs. 0.17 +/- 0.08 ng/mL in control rats, p < 0.05) after a single intramuscular injection. In the Bethesda assay, neutralizing antibodies for FVIII protein were detected only in FVIII-LV injected rats by the 10th week, but not in control rats. This study suggested that a single administration of an advanced generation LV carrying the human FVIII cDNA resulted in elevation of FVIII level in immune competent rats, and that this gene transfer approach to the skeletal muscle could be an effective tool in treatment of hemophilia A.