Owing to its easy-to-use and multiplexing nature, the genome editing tool CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats (CRISPR) associated nuclease 9) is revolutionizing many areas of medical research and one of the most amazing areas is its gene therapy potentials. Previous explorations into the therapeutic potentials of CRISPR-Cas9 were mainly conducted in vitro or in animal germlines, the translatability of which, however, is either limited (to tissues with adult stem cells amenable to culture and manipulation) or currently impermissible (due to ethic concerns). Recently, important progresses have been made on this regard. Several studies have demonstrated the ability of CRISPR-Cas9 for in vivo gene therapy in adult rodent models of human genetic diseases delivered by methods that are potentially translatable to human use. Although these recent advances represent a significant step forward to the eventual application of CRISPR-Cas9 to the clinic, there are still many hurdles to overcome, such as the off-target effects of CRISPR-Cas9, efficacy of homology-directed repair, fitness of edited cells, immunogenicity of therapeutic CRISPR-Cas9 components, as well as efficiency, specificity, and translatability of in vivo delivery methods. In this article, we introduce the mechanisms and merits of CRISPR-Cas9 in genome editing, briefly retrospect the applications of CRISPR-Cas9 in gene therapy explorations and highlight recent advances, later we discuss in detail the challenges lying ahead in the way of its translatability, propose possible solutions, and future research directions.

Objective : To investigate effects of hydrogen-rich water (HRW) on oxidative stress, liver function and HBV DNA in patients with chronic hepatitis B (CHB). Methods : Sixty patients with CHB were randomly assigned into routine treatment group or hydrogen treatment group in which patients received routine treatment alone or additional oral HRW (1200-1800 mL/day, twice daily), respectively, for 6 consecutive weeks. Serum oxidative stress, liver function, and HBV DNA level were detected before and after treatment. Thirty healthy subjects served as controls.Results : When compared with controls, oxidative stress was obvious in CHB patients, and the liver function also signifi cantly impaired. After treatment, the oxidative stress remained unchanged in routine treatment group, but markedly improved in hydrogen treatment group. The liver function was improved signifi cantly and the HBV DNA reduced markedly after corresponding treatments. Although a signifi cant difference was noted in the oxidative stress between two groups after treatment, the liver function and HBV DNA level were comparable after treatment and both had improved tendencies. Conclusion : HRW signifi cantly attenuates oxidative stress in CHB patients, but further study with long-term treatment is required to confi rm the effect of HRW on liver function and HBV DNA level. Clin Trans Sci 2013; Volume 6: 372-375

Liver cancer is one of the most common malignant tumors, and most of which is hepatocellular carcinoma (HCC). We aim to study the characteristic changes of numerous genes and their roles in HCC through systematical analysis of the characteristics of expression spectrum of HCC. Firstly, we made systematic clustering of the HCC samples according to the RNAseq data from TCGA (The Cancer Genome Atlas) and newly classified HCC. Then the characteristic genes in different molecular subtypes were found out and further analyzed combing with methylation and SNP 6.0 chip. Finally, these genes were subjected to do functional annotation and abnormal signaling pathways of HCC in various molecular subtypes and were screened out. There were 3843 differential genes screened; among which, 689 genes were enriched into 13 KEGG-related pathways, and the expression of 27 and 924 genes showed positive and negative correlation to methylation level, respectively, while the expression of 43 genes showed positive correlation to variation level of copy number. The methylation degree of ZSCAN18 may be considered as a marker for prognosis evaluation, and ABHD6 could be a potential anti-oncogene.

Long noncoding RNAs (lncRNAs) have been demonstrated to play significant roles in hepatocellular carcinoma (HCC) tumor progression. LINC01433 has been implicated in the progression of lung cancer. However, its biological role in HCC remains poorly understood. In our current study, we focused on the detailed mechanism of LINC01433 in HCC development. First, it was exhibited that LINC01433 was remarkably elevated in HCC cells, which indicated that LINC01433 was involved in HCC. Then, knockdown of LINC01433 was able to restrain HCC cell proliferation and cell colony formation and greatly induced cell apoptosis. On the contrary, overexpression of LINC01433 promoted HCC cell proliferation, increased cell colony formation, and enhanced cell invasion capacity. Subsequently, we found that miR-1301 was remarkably decreased in HCC cells, and it can serve as a target of LINC01433 according to bioinformatics analysis. In addition, the binding correlation between them was validated by performing RNA pull-down experiments and RIP assay. Moreover, STAT3 was predicted and validated as a target of miR-1301, and it was shown that miR-1301 mimics significantly suppressed STAT3 in HCC cells.Finally, in vivo models were established, and the results demonstrated that silencing of LINC01433 could repress HCC development through modulating miR-1301 and STAT3. Taken together, these results indicated in our study that LINC01433 participated in HCC progression through modulating the miR-1301/STAT3 axis and it might act as a novel biomarker in HCC diagnosis and treatment.