Fig. 1: Tissue-selective gene therapies reverse hyperglycaemia in SKO mice.
From: Preclinical evaluation of tissue-selective gene therapies for congenital generalised lipodystrophy
A Viral vector plasmid design to overexpress the long form of the human BSCL2 transcript (NM_001122955.4) driven by the adipose-selective mini/aP2 (pAAV8-mini/aP2-hBSCL2) or liver-selective thyroxine binding globulin (pAAV8-TBG-hBSCL2) promoters. B Weight gain progression in wild type (WT) and seipin knockout (SKO) mice after I.P. injection of 1 × 1012 genome copies of AAV8 vectors containing GFP (AAV-GFP), or human BSCL2 under control of the CMV (AAV-CMV), mini/aP2 (AAV-aP2) or TBG promoter (AAV-TBG). Whole body fat mass (C) and whole body lean mass (D) levels normalised to body weight and assessed by EchoMRI 4 and 8 weeks after AAV administration. E Blood glucose levels in ad lib fed WT, AAV-GFP, AAV-CMV, AAV-aP2 and AAV-TBG treated mice at 4 and 8 weeks after administration of gene therapy. All data are biological replicates presented as the mean ± SD, n = 44 (WT), 14 (AAV-GFP), 5–6 (AAV-CMV), 5 (AAV-aP2) and 5 (AAV-TBG) mice per group, *p < 0.05, **p < 0.01, ***p < 0.001 and ****p < 0.0001 vs. WT, #p < 0.05, ##p < 0.01, ###p < 0.001 and ####p < 0.0001 vs. AAV-GFP.
