In 1998 RNAi was discovered as a novel way of inhibiting protein expression and in the last decade has resulted in many novel insights in fundamental biological processes. An important contribution for the application of RNAi came from Craig Mellow and Andrew Fire, which both received the Nobel price of Physiology or Medicine in 2006.

Many advances have also occurred in the last 100 years toward understanding CNS related illnesses. Unfortunately the development of novel therapies for CNS related diseases falls behind. An important first step is improvement of validation assays to identify potential novel drug targets. This consortium hopes to contribute to this development by applying the latest RNAi technologies.

Specific CNS gene knock-down in rats as well as conditional gene knock-down in mice using various state of the art technologies are set up. In the future these methods will be applied to identify novel targets for CNS related diseases. Also specific target proteins were identified for effectively blocking neuroblastoma cell growth, the most common form of cancer of neurological origin in infancy. A peptide/siRNA complex was successfully tested for its potential to block cancer cell growth and patent filing is currently investigating.

Fast Facts
Full project title: CNS drug target validation using RNA interference
Project theme: CNS, Brain
Start date: april 2008
End date: april 2012
Goal: Drug target validation in CNS related disease
Principal investigator: Roger Adan, Utrecht University
Project size: 8 fte
Partners: UvA, Utrecht University, Leiden University, Organon, Prosensa Therapeutics.


The central nervous system (CNS) is part of the nervous system containing the brain and the spinal cord. The CNS coordinates and integrates the different signals it receives from other parts of the body. Since the CNS basically allows the body to function, CNS related diseases can have serious consequences.
Many advances however have occurred in the last 100 years toward better understanding of CNS related illnesses. In the post-genomic era many novel disease related genes have been identified by comparative genetic analysis. These studies have not only given us novel insights in the pathogenesis of CNS related disorders but also left us with a substantial list of putative drug targets. Therefore much research effort is currently put into functional analysis and validation of these novel targets. 

RNA interference is one of the major discoveries in biomedical sciences of the last decade. RNAi mediated gene inhibition has led to numerous novel insights in fundamental biological processes. The application of RNAi in drug discovery is twofold; on the one hand short interfering RNA’s offer a novel tool in gene validation studies by rapidly and specifically inhibiting gene expression. On the other hand, the shRNA molecules on  itself could be used as potent novel agents inhibiting gene function and thereby holding the promise of potential novel therapeutics in CNS related diseases.  

PhD theses from this project

Dirk-Jan Saaltink (project T5-210)
Doublecortin-like knockdown in adult mouse brain

“TI Pharma has developed frameworks in which academia and industry bring their ideas together and they work on the best ideas together.”

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