Pharmaceutical Gene Modulation  

The elucidation of the complete human genome with approximately 25.000 different genes will lead to new possibilities for diagnosis and prevention of a wide variety of diseases. In addition, this knowledge may be used for the design of new therapeutics, based on the DNA sequence information.

The research in the department of Pharmaceutical Gene Modulation (PGM) is focused on the development of medicines for the therapeutic manipulation of gene activity. Genetic drugs and delivery forms are being developed for the specific and efficient treatment of different diseases. Currently, the research is focused on cancer and inflammatory diseases.

One of the most efficient means of transferring genetic information is by using viral vectors. Unfortunately, the use of these vectors is not without danger partly because the majority of the vector ends up in the liver. Therefore, the transduction pattern and/or the expression of the transgene needs to be restricted to target cells. Apart from potentially dangerous aspecificity, gene therapy suffers from a lack of efficiency.

These aspects; efficiency and specificity of gene transfer, are the main focus of the research in the department of therapeutic gene modulation and are investigated on three levels: a) transductional retargeting (the vector recognizes specific cell types), b) transcriptional retargeting (the transgene product is only produced in target cells) en c) transgene transmission (efficient spread of the gene product).

A second line of research is the development of small molecules for modulation of the activity of transcription factors in order to modulate gene expression. The histone acetyltransferases are targets for inhibition. Small molecules inhibitors are developed using a medicinal chemistry approach including molecular modeling, organic synthesis and enzyme inhibition studies. The inhibitors will be applied in a reverse chemical genetics approach to study the role of histone acetyltransferases in gene transcription in more detail, which will ultimately result in therapeutic applications.

The research covers the complete route in the use and development of molecular therapeutics (medicinal chemistry, chemical synthesis), cloning of efficient gene therapy vectors (molecular biology) and testing in cell lines and animal models. Further information can be obtained from Prof. Dr. Hidde Haisma (h.j.haisma@rug.nl) or Dr. Frank Dekker (f.j.dekker@rug.nl)  tel 3637866.