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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Jeon
Hyun Jeong
HJ
Department of Internal Medicine, Chungbuk National University School of Medicine, Cheongju, Korea.
Oh
Tae Keun
TK
Kim
Oak Hee
OH
Kim
Seung Taik
ST
D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D005169:Factor VIII / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D006367:HeLa Cells; D006467:Hemophilia A / Q000628:therapy; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014161:Transduction, Genetic; D001616:beta-Galactosidase
D000906:Antibodies; D005169:Factor VIII; D001616:beta-Galactosidase