Nucleic acid therapeutics have demonstrated an impressive acceleration in recent years. They work through multiple mechanisms of action, including the downregulation gene expression and modulation RNA splicing. While several drugs based on former mechanism been approved, few target latter, despite promise splicing modulation. To improve our ability to discover novel splicing-modulating therapie...

Polycomb response elements (PREs) are cis-regulatory sequences required for Polycomb repression of Hox genes in Drosophila. PREs function as potent silencers in the context of Hox reporter genes and they have been shown to partially repress a linked miniwhite reporter gene. The silencing capacity of PREs has not been systematically tested and, therefore, it has remained unclear whether only spe...

KAL1 is implicated in 5% of Kallmann syndrome cases, a disorder which genotypically overlaps with septo-optic dysplasia (SOD). To date, a reporter-based assay to assess the functional consequences of KAL1 mutations is lacking. We aimed to develop a luciferase assay for novel application to functional assessment of rare KAL1 mutations detected in a screen of 422 patients with SOD. Quantitative a...

A vital step in transgenic animal study and gene therapy is the ability to assay the extent of transgene expression. Unfortunately, classic methods of assaying transgene expression require biopsies or death of the subject. We are developing techniques to noninvasively and repetitively determine the location, duration, and magnitude of transgene expression in living animals. This will allow inve...

Highly sensitive reporter-gene assays have been developed that allow the precise quantification of both direct vascular endothelial growth factor-A neutralizing activity bevacizumab and ability to activate antibody dependent cellular cytotoxicity. The use these analyzes samples from patients with ovarian cancer following four cycle treatment revealed a close correlation between cytotoxicity act...

Abstract The study has developed a model splicing construct assay system based on misregulation, one of the major molecular features associated with myotonic dystrophy. double reporters for intron 2 in chloride channel (CLCN1). CLCN1 transgene was used to transfect wild type and DM fibroblast cell lines clones generated showed that it enabled quantification efficiency construct. Validation fibr...

Abstract Background Endometrial cancer is an invasive gynecological prevalent in the world. The pathogenesis of endometrial related to multiple levels regulation, referring oestrogen, tumor-suppressor gene (e.g. PTEN ) or microRNAs miR-23a and miR-29b). Metapristone a hormone-related drug, which widely used clinical treatment cancer. However, underlying regulatory mechanism metapristone on stil...

Plasminogen activator inhibitor-1 (PAI-1) is an important regulator of numerous pathophysiological processes such as inflammation, thrombosis, angiogenesis and tumor metastasis. Its expression is induced by hypoxia at the transcriptional level, via the hypoxia inducible factor-1 (HIF-1) or -2 (HIF-2). In this study, we elucidated the mechanism of transcriptional regulation of mouse PAI-1 gene b...