Belgium's Galapagos Genomics has unveiled a new RNA interference-based gene silencing technology, based on an adenovirus, that is able to knock out gene expression in a range of cell types.
The research, published in Genome Research, suggests that a mjor obstacle to the widespread use of RNAi in drug discovery efforts can be overcome using Galapagos' adenovirus-based approach.
RNAi is a powerful tool for studying gene function and for drug target discovery in diverse organisms and cell types and, in mammalian systems, small interfering RNAs (siRNAs), or DNA plasmids expressing them have been used to down-modulate gene expression.
However, inefficient transfection protocols, in particular for primary cell types, have hampered the use of these tools in disease-relevant cellular assays. To be able to use this technology for genome-wide function screening, a more robust transduction protocol, resulting in a longer duration of the knock-down effect, is required.
In the latest study, the Galapagos researchers describe the validation of adenoviral vectors which express hairpin RNAs that are further processed to siRNAs.
"Infection of cell lines or primary human cells with these viruses leads to a sequence-specific and prolonged reduction of the corresponding target mRNA, resulting in a reduction of the encoded protein level in the cell," said Galapagos.
Based on the published approach, Galapagos has built a collection of adenoviruses with knock down sequences targeting over 4,000 human druggable genes, i.e. those gene classes of most value for pharmaceutical development. This collection, called SilenceSelect, enables high throughput, functional discovery of genes using relevant cell assays, according to the firm.
Galapagos' is currently applying this collection to internal discovery programs that are focused on bone disorders and Alzheimer's disease. These programs have already resulted in identification of novel druggable targets and Galapagos said it now intends to seek third party partners for further drug development.
Meantime, the firm recently reached an important milestone in its first SilenceSelect agreement with a top tier pharmaceutical partner that was initiated in early 2003.