Cited 15 times in
Safety and efficacy of adeno-associated viral vector-mediated insulin gene transfer via portal vein to the livers of streptozotocin-induced diabetic Sprague-Dawley rats
DC Field | Value | Language |
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dc.contributor.author | 김경섭 | - |
dc.contributor.author | 안철우 | - |
dc.contributor.author | 이용호 | - |
dc.contributor.author | 이현철 | - |
dc.contributor.author | 차봉수 | - |
dc.date.accessioned | 2017-09-30T06:33:57Z | - |
dc.date.available | 2017-09-30T06:33:57Z | - |
dc.date.issued | 2005 | - |
dc.identifier.issn | 1099-498X | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/150041 | - |
dc.description.abstract | BACKGROUND: Previous studies demonstrating the efficacy of insulin gene therapy have mostly involved use of adenoviral vectors or naked DNA to deliver the insulin gene. However, this procedure may not guarantee long-term insulin production. To improve the performance, we prepared recombinant adeno-associated viral vectors (rAAV) harboring the gene encoding a furin-modified human insulin under the cytomegalovirus (CMV) promoter [rAAV-hPPI(F12)]. METHODS: Streptozotocin (STZ)-induced diabetic Sprague-Dawley rats were used as a diabetic animal model. The levels of blood glucose, insulin, and HbA1c were measured to test the effect. An intraperitoneal glucose tolerance test was performed to test the capability of blood glucose disposal. Immunohistochemical staining and Northern blot analyses were performed to survey the expression pattern of the therapeutic insulin gene. RESULTS: STZ-induced diabetic Sprague-Dawley rats infused via the portal vein with rAAV-hPPI(F12) produced human insulin and after a 6-h fast were normoglycemic for over 90 days post-treatment, whereas diabetic rats treated with recombinant adenoviral vector harboring the hPPI(F12) gene [rAV-hPPI(F12)] were normoglycemic only for days 3 to 13 post-treatment. Insulin mRNA was detected mainly in the liver of the rAAV-hPPI(F12)-treated diabetic rats. The glucose tolerance capability of the rAAV-hPPI(F12)-treated diabetic rats was comparable to that of non-diabetic rats, even without injection of recombinant insulin. Furthermore, blood HbA1c concentrations in rAAV-hPPI(F12)-treated diabetic rats were reduced to almost the normal level. Importantly, studies of rAV or rAAV vector-dependent side effects on the targeted liver strongly suggested that only rAAV treatment caused no side effects. CONCLUSIONS: These results demonstrate that our rAAV-mediated in vivo insulin gene therapy provides safer maintenance of the insulin gene expression required for long-term and thus more effective blood glycemic control. | - |
dc.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | John Wiley & Sons | - |
dc.relation.isPartOf | JOURNAL OF GENE MEDICINE | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Animals, Genetically Modified | - |
dc.subject.MESH | Blood Glucose/metabolism | - |
dc.subject.MESH | Cytoskeletal Proteins/pharmacology | - |
dc.subject.MESH | Dependovirus/genetics* | - |
dc.subject.MESH | Diabetes Mellitus, Experimental/metabolism | - |
dc.subject.MESH | Diabetes Mellitus, Experimental/therapy* | - |
dc.subject.MESH | Gene Transfer Techniques* | - |
dc.subject.MESH | Genetic Therapy* | - |
dc.subject.MESH | Genetic Vectors* | - |
dc.subject.MESH | Glucose Tolerance Test | - |
dc.subject.MESH | Glycated Hemoglobin A/metabolism | - |
dc.subject.MESH | Insulin/genetics* | - |
dc.subject.MESH | Insulin/metabolism | - |
dc.subject.MESH | Liver/metabolism* | - |
dc.subject.MESH | Male | - |
dc.subject.MESH | Portal Vein | - |
dc.subject.MESH | Proinsulin/metabolism | - |
dc.subject.MESH | Pyrin | - |
dc.subject.MESH | Rats | - |
dc.subject.MESH | Rats, Sprague-Dawley | - |
dc.subject.MESH | Safety | - |
dc.subject.MESH | Treatment Outcome | - |
dc.title | Safety and efficacy of adeno-associated viral vector-mediated insulin gene transfer via portal vein to the livers of streptozotocin-induced diabetic Sprague-Dawley rats | - |
dc.type | Article | - |
dc.publisher.location | England | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | Young Mi Park | - |
dc.contributor.googleauthor | Seonock Woo | - |
dc.contributor.googleauthor | Geun Taek Lee | - |
dc.contributor.googleauthor | Ji-Yun Ko | - |
dc.contributor.googleauthor | Yongho Lee | - |
dc.contributor.googleauthor | Zheng-Shan Zhao | - |
dc.contributor.googleauthor | Hye Joo Kim | - |
dc.contributor.googleauthor | Chul Woo Ahn | - |
dc.contributor.googleauthor | Bong Soo Cha | - |
dc.contributor.googleauthor | Kyung-Sup Kim | - |
dc.contributor.googleauthor | Cheol Won Park | - |
dc.contributor.googleauthor | Hyun Chul Lee | - |
dc.identifier.doi | 10.1002/jgm.708 | - |
dc.contributor.localId | A00297 | - |
dc.contributor.localId | A02270 | - |
dc.contributor.localId | A02989 | - |
dc.contributor.localId | A03301 | - |
dc.contributor.localId | A03996 | - |
dc.relation.journalcode | J01419 | - |
dc.identifier.eissn | 1521-2254 | - |
dc.identifier.pmid | 15651056 | - |
dc.identifier.url | http://onlinelibrary.wiley.com/doi/10.1002/jgm.708/abstract | - |
dc.subject.keyword | diabetes mellitus | - |
dc.subject.keyword | basal insulin | - |
dc.subject.keyword | gene therapy | - |
dc.subject.keyword | recombinant viral vectors | - |
dc.contributor.alternativeName | Kim, Kyung Sup | - |
dc.contributor.alternativeName | Ahn, Chul Woo | - |
dc.contributor.alternativeName | Lee, Yong Ho | - |
dc.contributor.alternativeName | Lee, Hyun Chul | - |
dc.contributor.alternativeName | Cha, Bong Soo | - |
dc.citation.volume | 7 | - |
dc.citation.number | 5 | - |
dc.citation.startPage | 621 | - |
dc.citation.endPage | 629 | - |
dc.identifier.bibliographicCitation | JOURNAL OF GENE MEDICINE, Vol.7(5) : 621-629, 2005 | - |
dc.date.modified | 2017-05-04 | - |
dc.identifier.rimsid | 42722 | - |
dc.type.rims | ART | - |
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