Expression Of The Human Dystrophin Gene In Mdc Mouse Muscle After Transfer With Liposomes Or Synthetic Oligopeptide Complex Vectors

The number of dysrophin-positive fibers appearing in the femoral quadriceps muscle of mdx mice after injection of the full-length human dystrophin cDNA within the pHSADy plasmid was examined by means of immunohystochemical techniques. Transfection was carried out using lipofectamine (LFA), or synthetic oligopeptide complexes that provided the condensation of plasmid DNA (K8) and its release from endosomes (JTS1), The LFA + pHSADy at a dose of 10 mu g DNA did not affect the number of dystrophyn-positive fibers at the site of injection (0.6-0.8%), whereas it caused a statistically significant increase in the number of these fibers in the same muscle of the contralateral leg (up to 2.3%). Injection of the SO + pHSADy complex resulted in the occurrence of dysrophin-positive muscle fibers characterized by a heterogeneous content and the distribution of dystrophin. The greatest number of dystrophin-positive fibers (about 16%) was observed under a ratio of pHSADy to K8 of 1 : 3 or 1 : 4. The observed maximal number of dystrophin-positive fibers after a single injection of SO + pHSADy was 3.8%, and it was 17.7% after three injections. These values were statistically significantly higher compared to intact mice (0.6%), the injection of pure plasmid (2.2%), or the intramuscular injection of sucrose (from 0.7 lo 1.3%). A relatively high level of transfection (about 5%) was observed after an intracardiac injection of a large dose of the pHSADy (70 mu g DNA). The perspectives of the targeted delivery of the dystrophin gene into muscles under conditions of parenteral administration are discussed.