Gene therapy to improve pancreatic islet transplantation for type 1 diabetes mellitus

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dc.contributor.authorHughes, A.
dc.contributor.authorJessup, C.
dc.contributor.authorDrogemuller, C.
dc.contributor.authorMohanasundaram, D.
dc.contributor.authorMilner, C.
dc.contributor.authorRojas-Canales, D.
dc.contributor.authorRuss, G.
dc.contributor.authorCoates, P.
dc.date.issued2010
dc.description.abstractPancreatic islet transplantation is a promising treatment option for Type 1 Diabetics, offering improved glycaemic control through restoration of insulin production and freedom from life-threatening hypoglycaemic episodes. Implementation of the Edmonton protocol in 2000, a glucocorticoid-free immunosuppressive regimen has led to improved islet transplantation success. >50% of islets are lost post-transplantation primarily through cytokine-mediated apoptosis, ischemia and hypoxia. Gene therapy presents a novel strategy to modify islets for improved survival post-transplantation. Current islet gene therapy approaches aim to improve islet function, block apoptosis and inhibit rejection. Gene transfer vectors include adenoviral, adeno-associated virus, herpes simplex virus vectors, retroviral vectors (including lentiviral vectors) and non-viral vectors. Adeno-associated virus is currently the best islet gene therapy vector, due to the vectors minimal immunogenicity and high safety profile. In animal models, using viral vectors to deliver genes conferring local immunoregulation, anti-apoptotic genes or angiogenic genes to islets can significantly improve islet survival in the early post-transplant period and influence long term engraftment. With recent improvements in gene delivery and increased understanding of the mechanisms underlying graft failure, gene therapy for islet transplantation has the potential to move closer to the clinic as a treatment for patients with Type 1 Diabetes.
dc.description.statementofresponsibilityHughes, Amy; Jessup, Claire; Drogemuller, Chris; Mohanasundaram, Daisy; Milner, Clyde; Rojas, Darling; R. Russ, Graeme; and T.H. Coates, Patrick
dc.identifier.citationCurrent Diabetes Reviews, 2010; 6(5):274-284
dc.identifier.doi10.2174/157339910793360897
dc.identifier.issn1573-3998
dc.identifier.issn1875-6417
dc.identifier.orcidJessup, C. [0000-0003-1184-6653]
dc.identifier.orcidDrogemuller, C. [0000-0001-9770-4845]
dc.identifier.urihttp://hdl.handle.net/2440/67093
dc.language.isoen
dc.publisherBentham Science Publishers Ltd.
dc.rightsEditors/Authors who publish in Bentham Journal/eBook will transfer copyright to their work to Bentham Science Publishers. Submission of a manuscript to the respective journals implies that all editors/authors have read and agreed to the content of the Covering Letter.
dc.source.urihttps://doi.org/10.2174/157339910793360897
dc.subjectGene therapy
dc.subjectIslet transplantation
dc.subjectType 1 diabetes
dc.subjectViral vectors
dc.subjectImmunomodulatory
dc.subjectAnti-apoptotic
dc.subjectAngiogenic
dc.subjectPancreatic Islet Transplantation
dc.subjectDiabetes Mellitus
dc.subjectcytokine-mediated apoptosis
dc.subjectadenoviral
dc.subjectadeno-associated virus
dc.subjectherpes simplex virus vectors
dc.subjectretroviral vectors
dc.subjectnon-viral vectors
dc.subjectApoptosis Protein
dc.subjectIslet Gene Therapy
dc.subjectAngiogenic Genes
dc.subjecttherapeutic technique
dc.subjectAdV-based vectors
dc.titleGene therapy to improve pancreatic islet transplantation for type 1 diabetes mellitus
dc.typeJournal article
pubs.publication-statusPublished

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