As the most concerned genetic defective disease, Duchenne-type muscular dystrophy has been attracting the attention of the international medical and biomedical community, and various new discoveries and breakthroughs are applied to DMD gene therapy at the first time. Just past the last day of 2015, the international authoritative journal Science, in one breath, published online three papers on the application of CRISPR/Cas9 gene editing technology to DMD gene therapy. The three papers were independently published by three U.S. research institutions (Harvard University, Duke University and the University of Texas) and were submitted at similar times. All three papers focus on the same topic, which is the application of gene editing technology for the treatment of DMD. The three papers have a lot in common: 1) they all use CRISPR/Cas9 technology for deletion gene editing; 2) they all use the most widely used animal model of DMD, the mdx mouse, for in vivo animal testing. mdx mice have a nonsense mutation in exon 23 of the DMD gene. The gene editing aims to completely delete this exon and create a permanent DMD gene without exon 23. 3, Both use the widely recognized AAV as a vehicle to transport the gene edited components into cells in vivo. 4, In addition to the observed improvement in muscle pathology – the reappearance of Dystrophin protein on muscle cell membranes – all three teams confirmed an increase in muscle strength in treated mice. 5, All did multiple administration methods, including local and intravenous intramuscular injections and intraperitoneal injections for systemic administration. 6, All confirmed that Dystrophin re-expression was seen in all muscles throughout the body, including the heart muscle, during systemic treatment. There are, however, some differences. Tabebordbar’s team at Harvard University, tried a single AAV9 vector to deliver all CRISPR/Cas9 gene editing components, but by comparison, the results were not as good as using two AAV9 vectors, delivering saCas9 and guide RNAs, respectively. in addition, a simultaneous trial of the tdTomato reporter gene was done, again confirming the in vivo gene editing feasibility. The AAV vector used by Nelson’s team at Duke University was AAV8, rather than AAV9, which is the usual choice for muscle tissue, and also achieved good results. The Long team at the University of Texas chose the larger classic spCas9 loaded into AAV9. It should be noted that this is a landmark result. The three teams achieved the same results, thus establishing the potential of CRISPR/Cas9 gene editing technology in the treatment of DMD. The advantages of this emerging treatment include: 1. The gene editing technology is done at the DNA level, and permanent results can be achieved with a single treatment. Unlike exon skipping, which requires long-term medication. The dystrophin protein that can be restored is closer to the full-length dystrophin protein and more functional than importing mini-dystrophin (or micro-dystrophin). 2. It will become standard practice for dual AAV vectors to carry CRISPR/Cas9 components separately, where AAV-saCas9 or AAV-spCas9 are universal components that can be applied to any disease and any mutation, and only different AAV-gRNAs need to be prepared to target different segments, thus treating different diseases and mutation types. It is favorable for mass production and cost reduction. In the case of DMD, almost all types of disease-causing mutations such as large fragment deletions, large fragment repeats, missense mutations, micro deletions, micro repeats, and shear site mutations may be improved by this therapeutic system. 3. AAV is a recognized safe vector and has been used in human clinical trials, and its safety will be further verified. Therefore, the combination of the two can be described as a perfect match, which will surely promote the gene therapy of gene defective diseases such as DMD at a rapid pace. Of course, there are still some imperfections in this new technology, and it needs to be optimized. First of all, the CRISPR/Cas9 gene editing system has a persistent problem of off-targeting, that is, there are unexpected DNA edits outside the expected editing region. These additional DNA edits may cause loss of function or over-activation of unrelated proteins, which can trigger unpredictable and serious side effects. Only through a more refined design that continuously reduces the off-target rate and takes into account the variability of different patients’ genomes can they be better used in the clinic. Secondly, AAV antibodies are already present in some human bodies, which will significantly affect the efficiency of targeted delivery of AAV vectors. Finally, although mdx mice are the most commonly used animal model for DMD, the clinical phenotype of mice lacking Dystrophin protein is much lighter than that of DMD patients, and does not affect the length of life at all. Therefore there is uncertainty about the real effect of formal application to patients. The vast differences between mouse models and large animals and humans have been seen many times before. The new year will surely herald new hope.