Antisense oligonucleotide-mediated alternative splicing has great potential for treatment of Duchenne muscular dystrophy (DMD) caused by mutations within nonessential regions of the dystrophin gene. We have recently shown in the dystrophic mdx mouse that exon 23, bearing a nonsense mutation, can be skipped after intramuscular injection of a specific 2 -O-methyl phosphorothioate antisense oligoribonucleotide (2OMeAO). This skipping created a shortened, but in-frame, transcript that is translated to produce near-normal levels of dystrophin expression. This expression, in turn, led to improved muscle function. However, because DMD affects muscles body-wide, effective treatment requires dystrophin induction ideally in all muscles. Here, we show that systemic delivery of specific 2OMeAOs, together with the triblock copolymer F127, induced dystrophin expression in all skeletal muscles but not in cardiac muscle of the mdx dystrophic mice. The highest dystrophin expression was detected in diaphragm, gastrocnemius, and intercostal muscles. Large numbers of fibers with near-normal level of dystrophin were observed in focal areas. Three injections of 2OMeAOs at weekly intervals enhanced the levels of dystrophin. Dystrophin mRNA lacking the targeted exon 23 remained detectable 2 weeks after injection. No evidence of tissue damage was detected after 2OMeAO and F127 treatment either by serum analysis or histological examination of liver, kidney, lung, and muscles. The simplicity and safety of the antisense protocol provide a realistic prospect for treatment of the majority of DMD mutations. We conclude that a significant therapeutic effect may be achieved by further optimization in dose and regime of administration of antisense oligonucleotide.exon skipping ͉ muscular dystrophy

This research article examines the impact of stock market capitalization on carbon emissions using forty high carbon-emitting countries from 1996 to 2018. This study adopts the Driscoll-Kraay method that simultaneously tackles heteroscedasticity, autocorrelation, and contemporaneous correlation issues. We find an inverted U relationship between stock market capitalization (SMC) and environmental degradation. We propose an extended environmental Kuznets curve based on SMC while energy intensity, industrialization, and urbanization increase emissions in sample countries. The quadratic method, SLM test, and derivative graphing detect the consensus of the inverted U relationship. The weak-negative SMC2 coefficient reveals that the dangerous impact of capitalization declines gradually and finally curbs the environmental degradation challenges. The relationship is strong in highly polluted countries with overvalued stock markets. The study catches no policy synergies between the growing stock market and increased carbon emissions. Stock market capitalization should be integrated into climate change adaptation strategies at national and regional levels, primarily to address the dark effect of environmental degradation.