Emd Millipore Corporation

M. L. Laboratories Plc

Innovata Limited

Kai S Lipinski

Lawrence S Young

Christopher J Wrighton

Steven Geraint Williams

Alistair Simpson Irvine

Robert L Crombie

The invention relates to improved genetic elements providing high levels of expression of operably-linked genes in a variety of tissues. In particular, fragments of unmethylated, CpG islands of less than 2 kb are shown to provide enhanced transgene expression and have advantages in terms of vector construction and cloning capacity.

Expression elements

Disclosed are DNA elements and constructs useful for obtaining tumor-selective gene expression in tumors having a mutated &#x3b2;-catenin/APC pathway. In particular, the use of these constructs to express genes encoding therapeutic proteins in colorectal cancer cells is described. The constructs comprise multiple repeats of a TCF-binding element operably linked to a promoter. By means of such a construct, tumor cell-specific expression of a prodrug-converting enzyme such as nitroreductase may be achieved. Coupled with systemic administration of a suitable prodrug, such as CB1954, selective killing of such tumor cells can be demonstrated.

Gene expression using T cell factor responsive element

Disclosed are DNA elements and constructs useful for obtaining tumour-selective gene expression in tumours having a mutated &bgr;-catenin/APC pathway. In particular, the use of these constructs to express genes encoding therapeutic proteins in colorectal cancer cells is described. The constructs comprise multiple repeats of a TCF-binding element operably linked to a promoter. By means of such a construct, tumour cell-specific expression of a prodrug-converting enzyme such as nitroreductase may be achieved. Coupled with systemic administration of a suitable prodrug, such as CB1954, selective killing of such tumour cells can be demonstrated.

TCF responsive element

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Staffordshire, United Kingdom

Kai S Lipinski