Systemic administration of HVJ viral coat-liposome complex containing human insulin vector decreases glucose level in diabetic mouse: A model of gene therapy.
In this study, we examined the feasibility of a systemic administration of HVJ-liposome complex containing human insulin construct into the blood in mice via the tail vein. Transfection of human insulin vector resulted in a transient decrease in serum glucose in streptozotocin (SZT)-induced diabetic mice, accompanied by the detection of human insulin in the liver and spleen. In accordance with the decreased glucose, plasma immunoreactive insulin could be detected up to 14 days after a single transfection in mice transfected with insulin vector. Repeated intravenous injection of human insulin vector every week resulted in a sustained decrease in serum glucose over a 4-week period, accompanied by the detection of C-peptide fragments and a significant decrease in BUN and creatinine. Here, we demonstrated the feasibility of intravenous systemic administration of an insulin vector that results in a sustained improvement of diabetic glucose metabolism.
Morishita
R
R
Division of Gene Therapy Science, Osaka University Medical School, Suita, 565-0871, Japan.
Gibbons
G H
GH
Kaneda
Y
Y
Ogihara
T
T
Dzau
V J
VJ
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D001483:Base Sequence; D001786:Blood Glucose / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000628:therapy*; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007275:Injections, Intravenous; D007328:Insulin / Q000235:genetics*; D008081:Liposomes / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018108:Respirovirus / Q000235:genetics; D014162:Transfection
D000952:Antigens, Polyomavirus Transforming; D001786:Blood Glucose; D017931:DNA Primers; D007328:Insulin; D008081:Liposomes