Lentivirus Mediated Pancreatic Beta-Cell-Specific Insulin Gene Therapy for STZ-Induced Diabetes.

Autor:	Erendor F; Department of Gene and Cell Therapy, Faculty of Medicine, Akdeniz University, Antalya 07058, Turkey., Eksi YE; Department of Gene and Cell Therapy, Faculty of Medicine, Akdeniz University, Antalya 07058, Turkey., Sahin EO; Department of Gene and Cell Therapy, Faculty of Medicine, Akdeniz University, Antalya 07058, Turkey., Balci MK; Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Akdeniz University, Antalya 07058, Turkey., Griffith TS; Department of Urology, School of Medicine, University of Minnesota, Minneapolis, MN 55455, USA., Sanlioglu S; Department of Gene and Cell Therapy, Faculty of Medicine, Akdeniz University, Antalya 07058, Turkey. Electronic address: ssanlioglu@icloud.com.
Jazyk:	angličtina
Zdroj:	Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2021 Jan 06; Vol. 29 (1), pp. 149-161. Date of Electronic Publication: 2020 Oct 31.
DOI:	10.1016/j.ymthe.2020.10.025
Abstrakt:	Autoimmune destruction of pancreatic beta cells is the characteristic feature of type 1 diabetes mellitus. Consequently, both short- and intermediate-acting insulin analogs are under development to compensate for the lack of endogenous insulin gene expression. Basal insulin is continuously released at low levels in response to hepatic glucose output, while post-prandial insulin is secreted in response to hyperglycemia following a meal. As an alternative to multiple daily injections of insulin, glucose-regulated insulin gene expression by gene therapy is under development to better endure postprandial glucose excursions. Controlled transcription and translation of proinsulin, presence of glucose-sensing machinery, prohormone convertase expression, and a regulated secretory pathway are the key features unique to pancreatic beta cells. To take advantage of these hallmarks, we generated a new lentiviral vector (LentiINS) with an insulin promoter driving expression of the proinsulin encoding cDNA to sustain pancreatic beta-cell-specific insulin gene expression. Intraperitoneal delivery of HIV-based LentiINS resulted in the lowering of fasting plasma glucose, improved glucose tolerance and prevented weight loss in streptozoticin (STZ)-induced diabetic Wistar rats. However, the combinatorial use of LentiINS and anti-inflammatory lentiviral vector (LentiVIP) gene therapy was required to increase serum insulin to a level sufficient to suppress non-fasting plasma glucose and diabetes-related inflammation. (Copyright © 2020 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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