Reversal of diabetes through gene therapy of diabetic rats by hepatic insulin expression via lentiviral transduction.

Molecular Therapy : the Journal of the American Society of Gene Therapy
Matthias ElsnerSigurd Lenzen

Abstract

Due to shortage of donor tissue a cure for type 1 diabetes by pancreas organ or islet transplantation is an option only for very few patients. Gene therapy is an alternative approach to cure the disease. Insulin generation in non-endocrine cells through genetic engineering is a promising therapeutic concept to achieve insulin independence in patients with diabetes. In the present study furin-cleavable human insulin was expressed in the liver of autoimmune-diabetic IDDM rats (LEW.1AR1/Ztm-iddm) and streptozotocin-diabetic rats after portal vein injection of INS-lentivirus. Within 5-7 days after the virus injection of 7 × 10(9) INS-lentiviral particles the blood glucose concentrations were normalized in the treated animals. This glucose lowering effect remained stable for the 1 year observation period. Human C-peptide as a marker for hepatic release of human insulin was in the range of 50-100 pmol/ml serum. Immunofluorescence staining of liver tissue was positive for insulin showing no signs of transdifferentiation into pancreatic β-cells. This study shows that the diabetic state can be efficiently reversed by insulin release from non-endocrine cells through a somatic gene therapy approach.

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Citations

Oct 16, 2012·Expert Reviews in Molecular Medicine·Ahter D SanliogluSalih Sanlioglu
Sep 20, 2012·Journal of Molecular Endocrinology·Ahter D SanliogluSalih Sanlioglu
Oct 10, 2013·EMBO Molecular Medicine·Kerstin B KaufmannManuel Grez
Jan 8, 2013·The Journal of Gene Medicine·Binhai RenAnn M Simpson
Jun 2, 2015·Molecular Therapy. Methods & Clinical Development·Janet LawandiAnn M Simpson
Apr 14, 2016·International Journal of Molecular Sciences·Binhai RenAnn M Simpson
May 26, 2016·Scientific Reports·Wenlong BaoYinglang Wan
Feb 8, 2018·Human Gene Therapy·Hale M TasyurekSalih Sanlioglu
Aug 16, 2017·Nature Reviews. Gastroenterology & Hepatology·Cara EllisTimothy J Kieffer
Apr 20, 2017·Frontiers in Psychiatry·Peter de HaanBert A 't Hart
Jun 13, 2018·Frontiers in Immunology·Miguel G Toscano, Peter de Haan
Nov 2, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Fulya ErendorSalih Sanlioglu
Apr 24, 2021·Redox Biology·Christina KrügerMatthias Elsner
May 15, 2021·Open Life Sciences·Arome Solomon OdibaYanjun Wu

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