Translational research : the journal of laboratory and clinical medicine
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Targeted nucleases are widely used as tools for genome editing. Two years ago the clustered regularly interspaced short palindromic repeat (CRISPR)-associated Cas9 nuclease was used for the first time, and since then has largely revolutionized the field. ⋯ Several studies recently used CRISPR/Cas9 to successfully modulate disease-causing alleles in vivo in animal models and ex vivo in somatic and induced pluripotent stem cells, raising hope for therapeutic genome editing in the clinics. In this review, we will summarize and discuss such preclinical CRISPR/Cas9 gene therapy reports.
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Recent efforts to broadly apply genetics to clinical practice have been driven by the rapid advancement of genomic technologies and the discovery of genes associated with disease risk, progression, and treatment response. Yet there remain valid concerns about the complexities and limitations that confront the popular notion of clinical utility of genetics in personalized medicine. ⋯ The excitement of discovery and applications to diagnostics are well described in each of the articles in this issue. Yet, each article appropriately acknowledges the limitations that need to be overcome to apply new knowledge to clinical practice.
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Recent studies have shown that long noncoding RNAs (lncRNAs) play crucial roles in human cancers. However, the function of lncRNAs and their downstream mechanisms are largely unknown in the molecular pathogenesis of intrahepatic cholangiocarcinoma (ICC). In the present study, we performed transcriptomic profiling of ICC and paired adjacent noncancerous tissues (N) by using lncRNA and messenger RNA (mRNA) microarrays. ⋯ Our results suggested that the lncRNA expression profiling in ICC tissues is profoundly different from that in noncancerous tissues. Thus, lncRNA may be a potential diagnostic and prognostic biomarker for ICC. Furthermore, the combined assessment of lncRNA and mRNA expressions might predict the survival of patients with ICC.
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The advent of high-throughput technologies has provided exceptional assistance for lung scientists to discover novel genetic variants underlying the development and progression of complex lung diseases. However, the discovered variants thus far do not explain much of the estimated heritability of complex lung diseases. Here, we review the literature of successfully used genome-wide association studies (GWASs) and identified the polymorphisms that reproducibly underpin the susceptibility to various noncancerous complex lung diseases or affect therapeutic responses. ⋯ Next, we describe the contribution of the metagenomics to understand the interactions of the airways microbiome with lung diseases. We then highlight the urgent need for new integrative genomics-phenomics methods to more effectively interrogate and understand multiple downstream "omics" (eg, chromatin modification patterns). Finally, we address the scarcity of genetic studies addressing under-represented populations such as African Americans and Hispanics.