Switching tumour fighters on and off
Biochemists from Konstanz develop genetic switch to control cancer-fighting viruses
Biochemists at the University of Konstanz and the German Cancer Research Center (DKFZ) in Heidelberg succeeded in controlling oncolytic viruses – i.e. viruses that destroy cancer cells – via a genetic switch. The Konstanz-based research unit, led by Professor Dr. Jörg Hartig, developed an artificial RNA switch that, in contrast to previous genetic switches, does not need the so-called transcription factor and thus allows the simple and precise control of gene expression in any organism. The research results, with great potential for cancer research, have been published in the renowned scientific journal "Proceedings of the National Academy of Sciences" (PNAS) at the beginning of February.
Prof. Dr. Jörg Hartig
So-called genetic switches offer the possibility to control which gene gets expressed in a cell and which features a cell has: genes can be switched on and off, enabling us to "programme" cells. Gene expression comprises two steps: first the genetic material in form of deoxyribonucleic acid (DNA) is transcribed into ribonucleic acid (RNA), which is then translated into a protein sequence in the cell. Previous genetic switches mostly affect the first step in this process, altering expression via the so-called transcription factor. "Systems based on the transcription factor are basically very effective, however, there are some disadvantages: the concentration of the transcription factor needs to be delicately balanced out, which means that these systems do not function as well in virus systems whose multiplication is subject to large fluctuations", explains Jörg Hartig
Together with his research unit, the biochemist from Konstanz succeeded in developing artificial RNA switches that are not affected by such fluctuations, which is why they can also be used to control e.g. several viruses. "Our artificial RNA switches do not need such transcription factors. This makes the system simpler and more precise, as the control takes place at the level of RNA: our switches are part of the protein-coding RNA", explains Hartig.
Oncolytic viruses can now be controlled with the help of this switch, too, thus providing great potential for cancer research: oncolytic viruses specifically attack cancer cells and destroy them. Hartig's genetic switch is a safety feature for the use of oncolytic viruses, preventing that the multiplication of the viruses gets out of control.
Controlling oncolytic viruses is not the only possible application for Hartig's genetic switch. "Our switches are remarkably versatile. The high modularity of the RNA switches allows us to use them in a great variety of organisms, for example, in viruses, bacteria, yeasts or mammalian cells", adds Hartig.
P. Ketzer et al.: Artificial riboswitches for gene expression and replication control of DNA and RNA viruses, PNAS 2014, 111, E554–E562, doi: 10.1073/pnas.1318563111