Selective inhibition of disease-related proteins underpins the majority of successful drug-target interactions. However, development of effective antagonists is often hampered by targets that are not druggable using conventional approaches. Here, we apply engineered zinc-finger protein transcription factors (ZFP TFs) to the endogenous phospholamban (PLN) gene, which encodes a well validated but...

Regulation of endogenous gene expression has been achieved using synthetic zinc finger proteins fused to activation or repression domains, zinc finger transcription factors (TFZFs). Two key aspects of selective gene regulation using TFZFs are the accessibility of a zinc finger protein to its target DNA sequence and the interaction of the fused activation or repression domain with endogenous pro...

BACKGROUND Stellate ganglion block (SGB) causes vasodilatation in the skin of the head and neck because of regional sympathetic block. Its effects on cerebral haemodynamics, in health or in disease, are not clear. We evaluated the effects of SGB on ipsilateral middle cerebral artery flow velocity (MCAFV), estimated cerebral perfusion pressure (eCPP), zero flow pressure (ZFP), carbon dioxide rea...

Peripheral arterial disease is a major complication of diabetes. The ability to promote therapeutic angiogenesis may be limited in diabetes. Type 2 diabetes was induced by high-fat feeding C57BL/6 mice (n = 60). Normal chow-fed mice (n = 20) had no diabetes. Mice underwent unilateral femoral artery ligation and excision. A plasmid DNA encoded an engineered transcription factor designed to incre...

Telomerase activation is a key step in the development of human cancers. Expression of the catalytic subunit, human telomerase reverse transcriptase (hTERT), represents the limiting factor for telomerase activity. In this study, we have used artificial zinc finger protein (ZFP) transcription factors (TF) to repress the expression of hTERT in human cancer cell lines at the transcriptional level....

UNLABELLED The human epidermal growth factor receptor-2 (HER2/neu/ERBB2) is overexpressed in several cancer types. Although therapies targeting the HER2/neu protein result in inhibition of cell proliferation, the anticancer effect might be further optimized by limiting HER2/neu expression at the DNA level. Towards this aim, epigenetic editing was performed to suppress HER2/neu expression by ind...

Zinc Finger Targeter (ZiFiT) is a simple and intuitive web-based tool that facilitates the design of zinc finger proteins (ZFPs) that can bind to specific DNA sequences. The current version of ZiFiT is based on a widely employed method of ZFP design, the ‘modular assembly’ approach, in which pre-existing individual zinc fingers are linked together to recognize desired target DNA sequences. Seve...