A cure for diabetes has long been sought using several different approaches, including islet transplantation, regeneration of β cells and insulin gene therapy1. However, permanent remission of type 1 diabetes has not yet been satisfactorily achieved. The development of type 1 diabetes results from the almost total destruction of insulin-producing pancreatic β cells by autoimmune responses specific to β cells2,3,4,5,6. Standard insulin therapy may not maintain blood glucose concentrations within the relatively narrow range that occurs in the presence of normal pancreatic β cells7. We used a recombinant adeno-associated virus (rAAV) that expresses a single-chain insulin analogue (SIA), which possesses biologically active insulin activity without enzymatic conversion, under the control of hepatocyte-specific L-type pyruvate kinase (LPK) promoter, which regulates SIA expression in response to blood glucose levels. Here we show that SIA produced from the gene construct rAAV-LPK-SIA caused remission of diabetes in streptozotocin-induced diabetic rats and autoimmune diabetic mice for a prolonged time without any apparent side effects. This new SIA gene therapy may have potential therapeutic value for the cure of autoimmune diabetes in humans.
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We thank R. J. Samulski for providing psub201 and pXX2, A. L. Kyle and K. Clarke for editorial assistance and B. Pinder for artwork. We also thank H. S. Jun for a critical review of the manuscript. J. W. Y. is a Heritage Medical Scientist awardee of the Alberta Heritage Foundation for Medical Research. This work was supported in part by Brain Korea 21 Project.
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Lee, H., Kim, SJ., Kim, KS. et al. Remission in models of type 1 diabetes by gene therapy using a single-chain insulin analogue. Nature 408, 483–488 (2000). https://doi.org/10.1038/35044106
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Retraction Note: Remission in models of type 1 diabetes by gene therapy using a single-chain insulin analogue