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Progress and prospects of engineered sequence-specific DNA modulating technologies for the management of liver diseases

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World Journal of Hepatology 2015年第6期7卷 859-873页

作者： Samantha A Nicholson Buhle Moyo Patrick B Arbuthnot Wits/SA MRC Antiviral Gene Therapy Research Unit School of Pathology Health Sciences Faculty University of the Witwatersrand

Liver diseases are one of the leading causes of mortality in the world. The hepatic illnesses, which include inherited metabolic disorders, hemophilias and viralhepatitides, are complex and currently difficult to treat. The maturation of gene therapy has heralded new avenues for developing effective intervention for these diseases. DNA modification using gene therapy is now possible and available technology may be exploited to achieve long term therapeutic benefit. The ability to edit DNA sequences specifically is of paramount importance to advance gene therapy for application to liver diseases. Recent development of technologies that allow for this has resulted in rapid advancement of gene therapy to treat several chronic illnesses. Improvements in application of derivatives of zinc finger proteins(ZFPs), transcription activator-like effectors(TALEs), homing endonucleases(HEs) and clustered regularly interspaced palindromic repeats(CRISPR) and CRISPR associated(Cas) systems have been particularly important. These sequence-specific technologies may be used to modify genes permanently and also to alter gene transcription for therapeutic purposes. This review describes progress in development of ZFPs, TALEs, HEs and CRISPR/Cas for application to treating liver diseases.

关键词： Gene therapy zinc fingers Transcriptionactivator-like effectors Clustered regularly interspacedshort palindromic repeats Homing endonucleases Liver diseases

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The C-terminal Binding Protein Co-Repressor(Ctbp) in the regulation of adipogenesis.

The C-terminal Binding Protein Co-Repressor(Ctbp) in the reg...

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第十七届国际生物物理大会;第十二届中国生物物理大会

作者： Merlin Crosslev Helen Williams Briony Jack Hannah Nicholas Kim Bell-Anderson School of Biotechnology and Biomolecular Science University of New South WalesSydneyAustralia2052 School of Molecular Bioscience University of SydneyAustralia2006

We have investigated gene regulatory proteins that influence differentiation of 3T3-L1 *** our experiments, forced expression of the DNA-binding transcription factors Basic Kruppel-like Factor/Kruppel-like Factor 3 (Klf3) and Gata2 can inhibit ***3 recruits the cofactor Ctbp,while Gata2 recruits Friend of Gatal (Fogl) and Fog2,which then recruit *** results suggest that Ctbp plays a role in adipogenesis but is required at only a subset of ***,we have extended our analysis of the metabolic phenotype of the Klf3 knockout mouse on conventional and high fat *** conclude that in vivo Klf3 deficiency affects white adipose tissue and glucose tolerance and in part protects from the effects of a high fat diet.

关键词： DNA-binding proteins Transcription factors zinc fingers Adipogenesis Ctbp

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