Degradable polymeric carrier for the delivery of IL-10 plasmid DNA to prevent autoimmune insulitis of NOD mice.
Recently, we have reported that biodegradable poly [alpha-(4-aminobutyl)-L-glycolic acid] (PAGA) can condense and protect plasmid DNA from DNase I. In this study, we investigated whether the systemic administration of pCAGGS mouse IL-10 (mIL-10) expression plasmid complexed with PAGA can reduce the development of insulitis in non-obese diabetic (NOD) mice. PAGA/mIL-10 plasmid complexes were stable for more than 60 min, but the naked DNA was destroyed within 10 min by DNase I. The PAGA/DNA complexes were injected into the tail vein of 3-week-old NOD mice. Serum mIL-10 level peaked at 5 days after injection, and could be detected for more than 9 weeks. The prevalence of severe insulitis on 12-week-old NOD mice was markedly reduced by the intravenous injection of PAGA/DNA complex (15.7%) compared with that of naked DNA injection (34.5%) and non-treated controls (90.9%). In conclusion, systemic administration of pCAGGS mIL-10 plasmid/PAGA complexes can reduce the severity of insulitis in NOD mice. This study shows that the PAGA/DNA complex has the potential for the prevention of autoimmune diabetes mellitus. Gene Therapy (2000) 7, 2099-2104.
Department of Pharmaceutics and Pharmaceutical Chemistry, Center for Controlled Chemical Delivery, University of Utah, Salt Lake City, UT 84112-5820, USA.
J J
JJ
Koh
K S
KS
Ko
M
M
Lee
S
S
Han
J S
JS
Park
S W
SW
Kim
D000818:Animals; D002460:Cell Line; D003850:Deoxyribonuclease I / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000628:therapy*; D004587:Electrophoresis, Agar Gel; D005260:Female; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage*; D007275:Injections, Intravenous; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics*; D008099:Liver / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D010957:Plasmids / Q000378:metabolism; D011100:Polyglycolic Acid / Q000031:analogs & derivatives*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection / Q000379:methods*
C414262:poly((4-aminobutyl)glycolic acid); D016753:Interleukin-10; D011100:Polyglycolic Acid; D003850:Deoxyribonuclease I