Gene therapy for diabetes mellitus in rats by intramuscular injection of lentivirus containing insulin gene
We assessed therapeutic potential of intramuscular insulin gene delivery in a diabetic murine model. The human proinsulin gene cDNA engineered with concensus furin cleavage sequences was inserted into an advanced lentiviral vector that contained CMV early promoter. After injection of concentrated le...
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| Vydáno v: | Diabetes research and clinical practice Ročník 71; číslo 3; s. 233 - 240 |
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Elsevier Ireland Ltd
01.03.2006
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| ISSN: | 0168-8227, 1872-8227 |
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| Abstract | We assessed therapeutic potential of intramuscular insulin gene delivery in a diabetic murine model. The human proinsulin gene cDNA engineered with concensus furin cleavage sequences was inserted into an advanced lentiviral vector that contained CMV early promoter. After injection of concentrated lentiviral vector (3.5
μg p24 Gag antigen) carrying the insulin gene into the thigh muscle, treated rats demonstrated an increase in body weight, increased survivability, attenuated the hyperglycemic response as well as prevented the formation of ketoacidosis. For these reasons, the intraparenchymal injection of lentiviral vectors into the skeletal muscle to ectopically produce insulin may be an easy and therapeutic treatment modality for type 1 diabetes mellitus. |
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| AbstractList | We assessed therapeutic potential of intramuscular insulin gene delivery in a diabetic murine model. The human proinsulin gene cDNA engineered with concensus furin cleavage sequences was inserted into an advanced lentiviral vector that contained CMV early promoter. After injection of concentrated lentiviral vector (3.5
μg p24 Gag antigen) carrying the insulin gene into the thigh muscle, treated rats demonstrated an increase in body weight, increased survivability, attenuated the hyperglycemic response as well as prevented the formation of ketoacidosis. For these reasons, the intraparenchymal injection of lentiviral vectors into the skeletal muscle to ectopically produce insulin may be an easy and therapeutic treatment modality for type 1 diabetes mellitus. We assessed therapeutic potential of intramuscular insulin gene delivery in a diabetic murine model. The human proinsulin gene cDNA engineered with concensus furin cleavage sequences was inserted into an advanced lentiviral vector that contained CMV early promoter. After injection of concentrated lentiviral vector (3.5 microg p24 Gag antigen) carrying the insulin gene into the thigh muscle, treated rats demonstrated an increase in body weight, increased survivability, attenuated the hyperglycemic response as well as prevented the formation of ketoacidosis. For these reasons, the intraparenchymal injection of lentiviral vectors into the skeletal muscle to ectopically produce insulin may be an easy and therapeutic treatment modality for type 1 diabetes mellitus.We assessed therapeutic potential of intramuscular insulin gene delivery in a diabetic murine model. The human proinsulin gene cDNA engineered with concensus furin cleavage sequences was inserted into an advanced lentiviral vector that contained CMV early promoter. After injection of concentrated lentiviral vector (3.5 microg p24 Gag antigen) carrying the insulin gene into the thigh muscle, treated rats demonstrated an increase in body weight, increased survivability, attenuated the hyperglycemic response as well as prevented the formation of ketoacidosis. For these reasons, the intraparenchymal injection of lentiviral vectors into the skeletal muscle to ectopically produce insulin may be an easy and therapeutic treatment modality for type 1 diabetes mellitus. We assessed therapeutic potential of intramuscular insulin gene delivery in a diabetic murine model. The human proinsulin gene cDNA engineered with concensus furin cleavage sequences was inserted into an advanced lentiviral vector that contained CMV early promoter. After injection of concentrated lentiviral vector (3.5 microg p24 Gag antigen) carrying the insulin gene into the thigh muscle, treated rats demonstrated an increase in body weight, increased survivability, attenuated the hyperglycemic response as well as prevented the formation of ketoacidosis. For these reasons, the intraparenchymal injection of lentiviral vectors into the skeletal muscle to ectopically produce insulin may be an easy and therapeutic treatment modality for type 1 diabetes mellitus. |
| Author | Li, Mei Zi Kim, Seung Taik Oh, Tae Keun |
| Author_xml | – sequence: 1 givenname: Tae Keun surname: Oh fullname: Oh, Tae Keun – sequence: 2 givenname: Mei Zi surname: Li fullname: Li, Mei Zi – sequence: 3 givenname: Seung Taik surname: Kim fullname: Kim, Seung Taik email: stkim@chungbuk.ac.kr |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/16171885$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.1038/sj.gt.3301544 10.1038/emm.2003.64 10.1006/bbrc.2000.2936 10.1038/35044106 10.1016/0014-5793(92)81366-T 10.1006/mthe.2001.0299 10.1210/me.11.6.833 10.1073/pnas.93.16.8595 10.1089/10430349950016672 10.1073/pnas.92.8.3293 10.1677/jme.0.0110335 10.1073/pnas.80.4.1068 10.1128/JVI.71.9.6641-6649.1997 10.1038/nbt1297-1378 10.1016/S0041-1345(97)00305-9 10.1016/S0014-5793(01)02352-3 10.1055/s-2007-979108 10.1038/sj.gt.3301297 10.2337/diabetes.41.8.956 10.2337/diabetes.51.1.130 10.1002/(SICI)1521-2254(199905/06)1:3<186::AID-JGM33>3.0.CO;2-W 10.1128/JVI.74.16.7642-7645.2000 10.1056/NEJM200007273430401 10.1016/S0021-9258(18)63828-1 10.1016/S0014-5793(01)03146-5 10.1126/science.283.5402.682 |
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| Keywords | Insulin gene therapy Lentivirus Intramuscular injection |
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| SubjectTerms | Animals Cell Line Diabetes Mellitus, Experimental - drug therapy Genes, Reporter Genetic Therapy - methods Genetic Vectors Green Fluorescent Proteins - genetics HeLa Cells Humans Injections, Intramuscular Insulin - administration & dosage Insulin - genetics Insulin - therapeutic use Insulin gene therapy Intramuscular injection Lentivirus Lentivirus - genetics Male Mice Proinsulin - genetics Promoter Regions, Genetic Rats Rats, Inbred F344 |
| Title | Gene therapy for diabetes mellitus in rats by intramuscular injection of lentivirus containing insulin gene |
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