CSIRO wins US patent for key RNAi vector

The legal mists swirling the issue of ownership of key patents to RNA-induced (RNAi) gene silencing are lifting, with the US Patent Office granting CSIRO a patent for its Hellsgate family of vectors for exploring and manipulating gene function in plants and animals.

Developed by CSIRO Plant Industry molecular geneticists Dr Chris Helliwell and Dr Peter Waterhouse, Hellsgate vectors are 'plug-and-play' molecular cassettes for knocking down target genes with great precision.

Helliwell works in the Plant Industry laboratory of Dr Peter Waterhouse, who, with colleague Dr Ming-Bo Wang, discovered RNAI-mediated gene silencing in plants in 1997.

Hellsgate vectors, which exploit Invitrogen's proprietary Gateway plug-and-play technology, accept cDNAs cloned from the messenger RNAs of genes of unknown function.

They automatically generate a 'designer' gene that, when inserted into the plant's cells by Agrobacterium tumifaciens, generates a palindromic messenger RNA. The mRNA folds back on itself and undergoes complementary base pairing, forming into a hairpin-shaped, double-stranded RNA that program the cell's RNA interference silencing complexes (RISCs), to knock down expression of the target gene.

The Hellsgate vector technology is almost 100 per cent efficient in generating hairpin molecules, but the efficiency of the knockdown effect varies according to the level of gene expression, and other factors.

CSIRO has made its proprietary technology available free to publicly funded plant genomics research institutions and universities around the world.

Plant Industry's business development manager, Dr Bill Taylor, said more than 2000 Hellsgate kits, and kits for its vector siblings, Stargate and Watergate, have been distributed to laboratories in Australia and overseas.

The major application for the vectors is in identifying genes involved in key traits such as pest and disease resistance, or tolerance of drought, heavy metal toxicity or salinity.

Taylor said CSIRO is actively licensing the technology for research, and the development of commercial products.

Europe's AGRIKOLA (Arabidopsis Genome RNAi Knock-Out Line Analysis) research consortium chose the Hellsgate vector system to explore and catalogue gene function in the plant geneticist's "green rat", Arabidopsis thaliana.

The consortium has developed some 20,000 "knockout" lines, one for each gene in Arabidopsis.

CSIRO and Brisbane gene therapy company Benitec (ASX:BLT) jointly own key patents on RNAi-mediated gene silencing; CSIRO has the right to exploit the patents for all applications in plant and animal research, while Benitec is focusing on human applications.