Benitec, CSIRO, QDPI resolve gene-silencing dispute

The big legal guns have fallen silent, and Queensland biotechnology company Benitec (ASX:BLT), CSIRO and Queensland's Department of Primary Industries have shaken hands on a landmark agreement that will allow CSIRO and Benitec to pursue their commercialisation of the revolutionary gene-silencing tool known as DNA-directed RNA interference (ddRNAi).

RNAi-mediated gene silencing is already widely used in public and private research around the world, and is regarded as the most powerful new tool to emerge from gene technology in the past decade.

Under their new agreement, Benitec will pursue human therapeutic applications of DDRNAi, CSIRO has the right to exploit its applications in non-human animals and plants, while QDPI will pursue its use in agricultural production systems, using either CSIRO or Benitec as commercialisation partners.

Benitec CEO Dr John McKinley said the agreement freed Benitec to pursue its strategic focus on the clinical development and commercialisation of human therapeutics, as well as giving his company a share of the revenues CSIRO develops from other applications.

CSIRO will in turn share revenues from Benitec's successful commercialisation of ddRNA, with each party retaining the majority of commercial revenues from its own applications.

Homegrown invention?

As the smoke clears, the basis of claims that the technology was invented in Australia has become clear.

The phenomenon of RNA interference was first observed in 1990 -- independently, by research teams in the US and Holland. But CSIRO's claim to priority, repeated in March this year, is that a Plant Industry research team led by Dr Peter Waterhouse discovered RNAi gene silencing in 1994 and performed the world's first ddRNAi gene-silencing experiment in any living organism in 1995.

Waterhouse's experiment involved introducing complementary transgenes containing genetic sequences of a tobacco virus into separate tobacco lines that were susceptible to the virus, then crossing them to produce fully resistant progeny.

A member of Waterhouse's team, Dr Mick Graham, left in 1996 to work with QDPI in Brisbane. Graham was the first to demonstrate ddRNAi-mediated gene silencing in mammalian cells, and this was the basis of a 1998 patent claim by QDPI and its commercial ally, Benitec. CSIRO filed its own patent a month later, in April, 1998.

An article in the August issue of Scientific American explained RNAI gene-silencing and chronicled its history, but failed to mention the Australian experiments that are claimed to have provided the first practical examples of RNAi-mediated gene silencing in plant and mammalian cells.

The international biotechnology company Syngenta, along with the Carnegie Institute in the US, have also filed patents around RNAi-mediated gene silencing techniques developed by some of the northern hemisphere research groups mentioned in the Scientific American article.

The patent claims at the heart of the now-resolved dispute between CSIRO and the Benitec/QDPI alliance all relate to ddRNAi silencing.

The DNA-directed technique relies on introducing transgenes into cells that can be designed to induce either transient or permanent silencing of a target gene.

The technique is claimed to be much more reliable, precise and versatile than other gene silencing techniques, including 'antisense' genes, or introducing siRNA -- short interfering RNAS -- into cells.

The power of the ddRNAi technique stems from researchers' ability to control both the timing and tissue-specific expression of the gene constructs.

'Completely resolved'

A joint statement issued by CSIRO, Benitec and QDPI late yesterday said the new agreement "completely resolves" their dispute. It describes the achievements of the three claimants in glowing terms, but provides no details of the concessions made by the parties to resolve their conflicting claims.

Benitec's CEO, Dr John McKinley, said the deal "provides clear and certain commercialisation pathways for this technology".

Merdad Baghai, CSIRO's executive director of business development and commercialisation, said the agreement "exemplifies CSIRO's new 'can-do' approach to partnering with industry to unlock the value of our science".

Baghai said gene-silencing technology would be a key platform for Australian life sciences research over the next decade.

CSIRO, Benitec and QDPI say their agreement will accelerate Australia's lead in the global commercialisation of the ddRNAi technique, which they say is expanding rapidly, potentially generating marketing opportunities worth billions of dollars.