GENE THERAPY FOR DIABETES WITH CHITOSAN-DELIVERED PLASMID ENCODING GLUCAGON-LIKE PEPTIDE 1

摘要

Chitosan delivers a plasmid encoding Glucagon-Like Peptide 1 (GLP-1) to cells in a patient for gene therapy of diabetes. Chitosan is optimized for plasmid transfection by modulating three of its physico-chemical properties: degree of deacetylation (DDA), molecular weight (MW), and ratio of amines on chitosan to phosphates on DNA (N:P ratio), Chitosan 92-10-5 (DDA-MW-N:P) is more efficient than chitosans 80-10-10 and 80-80-5 in delivering a plasmid encoding luciferase or GLP-1(7-37) to cells. In the Zucker Diabetic Fatty (ZDF) rat model of diabetes, chitosan-delivered pVax plasmid encoding GLP-1 lowers glucose levels, increases insulin production and reduces weight gain.