Gene silencing: Scientists specifically
deactivate virus DNA in human cells

Albert Jeltsch, IUB Professor of Biochemistry, and his co-workers from IUB, the Institute of Biochemistry of the University of Giessen, and the Medical Research Council of Cambridge University (UK) for the first time successfully used genetically engineered proteins to deactivate Herpes viruses in human cell lines. The artificial proteins attach methyl groups as markers at specific control areas of the DNA molecule, thereby repressing the activation of the genetic information of this region. The study is published in the current issue of Nucleic Acids Research (2006: doi:10.1093/nar/gkl1035).

[ Dec 06, 2006]  The human genom contains 20000-30000 genes as information units. These genes are specifically activated or deactivated by a process called “gene regulation“ according to the requirements of the developmental course of a human being. Special proteins, the DNA methyl transferases, play a central role in this process. They are targeted to gene sequences and attach methyl groups as markers to key sites on the DNA, which inhibit the reading and activation of the subsequent gene sequences. Methods of specifically silencing certain genes are of great interest for developing new therapeutic approaches, as many diseases such as cancer are characterized by the expression of ’disease genes’ or the expression of genes alien to the organism, as is a case with viral infections.

Albert Jeltsch and his co-workers now managed to genetically engineer artificial fusion proteins from catalytic components of DNA methyl transferases and various DNA site specific binding proteins. The components originated from mice, yeast or were completely artificially generated. The new fusion proteins are designed to target DNA control areas for binding and methylation with high specificity and repress gene activity. The scientists successfully applied the ‘designer enzymes’ to various systems, amongst them a culture of human cells infected with the Herpes virus HSV-1. The modified methyl transferases suppressed the virus infection by inhibiting its reproduction, which would have caused disease in a human body.

“Most pathological changes in organisms can be fought by suppressing the activity of critical ‘disease genes’. Therefore an efficient risk free external control of gene activity in the cells of an organism is a vision, which would completely change our approach to the therapy of many diseases”, Albert Jeltsch comments on the focus of the study. The data show that at least the problems of gene therapy regarding protein design are solvable, the IUB scientist continues. “Further studies will have to concentrate on improving the accessibility of as many target cells as possible for the artificial methyl transferases on the one hand. On the other hand the activity of the fusion proteins needs to be restricted to the relevant body tissues only, because a general inhibition of the targeted genes in the whole body in many cases is not desirable, as their activity might be vital for the organism in other physiological contexts.”