In vivo gene therapy of type I diabetic mellitus using a cationic emulsion containing an Epstein Barr Virus (EBV) based plasmid vector.
A cationic emulsion containing an insulin expression plasmid was prepared for the treatment of type 1 diabetic mellitus (DM) in vivo. A rat proinsulin-1 gene was inserted to EBV-based plasmid vectors containing CAG promoter. Cationic emulsion composed of DOTAP and squalene was complexed with the plasmid DNA. An intravenous injection of cationic emulsion containing proinsulin gene decreased blood glucose levels for 7 days within normal range. The cationic emulsion exerted more profound effect on blood glucose levels compared to naked DNA. RT-PCR results confirmed that the proinsulin was expressed in several organs containing liver, lung, spleen, and kidney. The refractory response was invoked by multiple injections of naked DNA or cationic emulsion/DNA complex, which was later proven to be an immune response against expressed proinsulin. Therefore, the cationic emulsion showed a promising result as a novel insulin gene therapy vehicle by decreasing blood glucose level for a month.
Yoo
Hyuk Sang
HS
Department of Biomaterials Engineering, School of Biotechnology and Bioengineering, Kangwon National University, Chunchon, 200-701 South Korea. hsyoo@kangwon.ac.kr
Mazda
Osam
O
Lee
Hyeon Yong
HY
Kim
Jin Chul
JC
Kwon
Seok Min
SM
Lee
Jung Eun
JE
Kwon
Ick Chan
IC
Jeong
Hesson
H
Jeong
Yu Seok
YS
Jeong
Seo Young
SY
D000818:Animals; D000906:Antibodies / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism / Q000628:therapy*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000378:metabolism / Q000628:therapy*; D004655:Emulsions; D015316:Genetic Therapy; D005822:Genetic Vectors; D004854:Herpesvirus 4, Human / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011384:Proinsulin / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D013311:Streptozocin; D013997:Time Factors; D014018:Tissue Distribution
D000906:Antibodies; D001786:Blood Glucose; D004655:Emulsions; D012333:RNA, Messenger; D013311:Streptozocin; D011384:Proinsulin