Figure 8.
Induction of the FXN Gene In Vivo in YG8R Mice Treated with AAV9 Expressing the plTALEST10X-6-15 or plTALEST10X-8-15 and AAV9 Expressing scFV-GFP-VP64
Mice were treated with two AAV9s (one containing scFV and the other one plTALEST10X-6-15 or plTALEST10X-8-15). To test potential synergistic effects of the combination of these two effectors, three AAV9 were used (AAV9-scFV, AAV9-plTALEST10X-6-15, and AAV-plTALEST10X-8-15). Several tissues were analyzed (muscle, heart, liver, and brain) in the treated mice and compared to those of control YG8R mice: untreated or treated with an AAV9, Ctrl (−), that did not express plTALEST10X. (A) Quantification of the number of FXN mRNAs by qRT-PCR in various organs of 3 different types of control mice and 4 groups of mice treated with the plTALEST10Xs. Additive and synergic effects were observed in muscles and heart when plTALEST10X-6 and plTALEST-10X-8 were used together. (B) The frataxin protein was significantly increased in muscle, heart, and liver of mice that received various plTALEST10X treatments. (C) Increased aconitase activity in the hearts of mice treated with AAV9-plTALEST10X-6-15 + AAV9-plTALEST10X-8-15 + pAAV-scFv plasmids. This increase is relative to negative controls (untreated mice) (n = 4). *p < 0.05, **p < 0.003, ***p < 0.0003, and ****p < 0.0001. (A–C) Results are the average ± SEM.