ArticleMolecular therapy : the journal of the American Society of Gene Therapy2008
AAV8-mediated gene transfer of interleukin-4 to endogenous beta-cells prevents the onset of diabetes in NOD mice.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 45 citations in OpenAlex.
- Role of Interleukins in Type 1 and Type 2 Diabetes.Diagnostics (Basel, Switzerland) · 2025Review
- A comprehensive atlas of AAV tropism in the mouse.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Exendin-4 protects β-cells against interleukin-1β-induced apoptosis via upregulating GMRP-1.American journal of translational research · 2025Article
- Inside the β Cell: Molecular Stress Response Pathways in Diabetes Pathogenesis.Endocrinology · 2022Review
- Co-opting regulation bypass repair as a gene-correction strategy for monogenic diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Cytokines in type 1 diabetes: mechanisms of action and immunotherapeutic targets.Clinical & translational immunology · 2020Review
- Safety and Efficacy of AAV Retrograde Pancreatic Ductal Gene Delivery in Normal and Pancreatic Cancer Mice.Molecular therapy. Methods & clinical development · 2018Article
- β-cell-specific IL-35 therapy suppresses ongoing autoimmune diabetes in NOD mice.European journal of immunology · 2017Article
- Article
- Protective role of adenovirus vector-mediated interleukin-10 gene therapy on endogenous islet β-cells in recent-onset type 1 diabetes in NOD mice.Experimental and therapeutic medicine · 2016Article
- Expression of IL-2 in β cells by AAV8 gene transfer in pre-diabetic NOD mice prevents diabetes through activation of FoxP3-positive regulatory T cells.Gene therapy · 2014Article
- A novel gene delivery method transduces porcine pancreatic duct epithelial cells.Gene therapy · 2014Article
- A practical guide to genetic engineering of pancreatic β-cells in vivo: getting a grip on RIP and MIP.Islets · 2014Review
- Review
- β-cell-specific IL-2 therapy increases islet Foxp3+Treg and suppresses type 1 diabetes in NOD mice.Diabetes · 2013Article
- dsAAV8-mediated gene transfer and β-cell expression of IL-4 and β-cell growth factors are capable of reversing early-onset diabetes in NOD mice.Gene therapy · 2012Article
- AAV2-mediated combined subretinal delivery of IFN-α and IL-4 reduces the severity of experimental autoimmune uveoretinitis.PloS one · 2012Article
- In vitro evaluation of a double-stranded self-complementary adeno-associated virus type2 vector in bone marrow stromal cells for bone healing.Genetic vaccines and therapy · 2011Article
- Genetic vaccination for re-establishing T-cell tolerance in type 1 diabetes.Human vaccines · 2011Review
- Adeno-associated virus-mediated IL-10 gene transfer suppresses lacrimal gland immunopathology in a rabbit model of autoimmune dacryoadenitis.Investigative ophthalmology & visual science · 2010Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
We have demonstrated the ability to deliver and express genes specifically in beta-cells for at least 6 months, using a murine insulin promoter (mIP) in a double-stranded, self-complementary AAV vector (dsAAV8-mIP). In this study, we evaluated the effects of dsAAV8-mIP-mediated delivery of interleukin 4 (mIL-4) to endogenous beta-cells in nonobese diabetic (NOD) mice. In 4-week-old NOD mice, the extent of gene transfer and expression in endogenous beta-cells after ip delivery of dsAAV8-mIP-enhanced green fluorescent protein (eGFP) was comparable to normal BALB/C mice. Further, after IP delivery of dsAAV8-mIP-IL4, expression of mIL-4 was detected in islets isolated from the treated mice and cultured. AAV8-mIP-mediated gene expression of mIL-4 in endogenous beta- cells of 4- and 8-week-old NOD mice prevented the onset of hyperglycemia in NOD mice and reduced the severity of insulitis. Moreover, expression of mIL-4 also maintained the level of CD4(+)CD25(+)FoxP3(+) cells, and adoptive transfer of splenocytes from nondiabetic dsAAV8-mIP-IL-4 mice to NODscid mice was able to block the diabetes induced by splenocytes co-adoptively transferred from nondiabetic dsAAV-mIP-eGFP mice. Taken together, these results demonstrate that local expression of mIL-4 in islets prevents islet destruction and blocks autoimmunity, partly through regulation of T-cell function.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.