Design and cellular delivery of a modified human deoxycytidine kinase with L-nucleoside analogue activity for use in cancer therapy

• Applicant: Dr. Theresa Schweizer
• Subject Area: Biochemistry
• Term: from 2010 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 160506553

Poor activation and off-target cytotoxicity often limit the efficacy of nucleoside analogue pro-drugs in the clinic. Our aim is to develop a therapeutic strategy which specifically targets tumour cells and increases the efficacy of nucleoside analogue pro-drugs in the treatment of certain cancers. We will modify the enzyme human deoxycytidine kinase (dCK) to enable it to exclusively phosphorylate and activate non-physiological L-nucleosides. The modified dCK will be targeted and delivered to tumour cells by the use of single chain antibodies (scFv) or affibodies. We propose that the confined delivery of our modified dCK to tumour cells and the use of L-nucleoside analogues will provide both increased cytotoxicity and increased specificity in nucleoside analogue chemotherapy.

• DFG Programme: Research Grants