Genera launches with PapTest

Molecular diagnostics has promised much for many years, but the full potential of the market is just being realised.

In June this year, US company Hologic announced it proposed to acquire another US company, Third Wave Technologies, for the reasonable sum of $580 million.

This follows the acquisition by German life sciences technology company Qiagen – which recently snapped up Australian instrument developer Corbett Life Sciences – of diagnostic pioneer Digene for US$1.6 billion.

Digene manufactures probably the most popular human papillomavirus diagnostic test on the market. Third Wave Technologies is also in the HPV field, set to shortly commercialise Cervista, its HPV test, which still subject to FDA approval.

The field is not limited to sexually transmitted diseases but these are the first cabs off the rank in molecular diagnostics, the future of which is unlimited.

Also in the field is Genera Biosystems, a newly listed company based in Melbourne that was set up to commercialise a portfolio of technologies originally developed by scientists from the Walter and Eliza Hall Institute, the Australian Genome Research Facility and the University of Melbourne.

Genera has developed a silica bead-based technology called AmpaSand that provides a full platform of DNA analysis technologies, initially focused on women’s health but promising a whole lot more.

Genera was initially spun out of WEHI in 2001 with a view to providing single nucleotide polymorphism (SNP) services to the academic community. This was never going to prove a competitive business in a growing field, but the SNP technology was always interesting from a diagnostic perspective.

Several years ago, Dr Karl Poetter, who had developed a process to detect SNPs by means of a different annealing temperature, called Sequence Identification by Flow Technology (SiFT) and was a founder of Genera, was approached by local pathology company Gribbles, now part of Healthscope, to help develop an HPV genotyping assay, which today has become PapTest.

PapTest is now available through Gribbles, which has validated the test using Australian Standards through NATA and the National Pathology Accreditation Advisory Council (NPAAC), but it is hoped the test will become more widely available after hoped-for approval from the TGA and in different jurisdictions next year.

Genera’s CEO, Dr Allen Bollands, says the technology differs from others in development and on the market because it is an all-in-one test with no requirement to buy expensive equipment to run the test.

For example, Digene’s test requires laboratories to buy not only the kit but the equipment to run it as well. Third Wave Technologies plans to initially screen patients for high-risk HPV using a non-genotyping test, and then genotype those specimens found to be high risk, looking for types 16 and 18, which cause 70 per cent of cervical cancers.

“Not only does PapType detect and genotype in a single test, it genotypes all 14 high-risk types of HPV, rather than just type 16 and 18,” Bollands says. “These other 12 high-risk types are responsible for approximately 30 per cent of all cervical cancers and the currently available vaccines offer, at best, limited protection against these types.”

Using Genera’s platform technology, the company is also developing a three-in-one STD test, to include the other big problems in sexual health, Chlamydia trachomatis and Neisseria gonorrhoea.

“The Chlamydia and gonorrhoea test is at a fairly advanced stage now and will have some advantages over existing CT/NG tests,” Bollands says.

“Those advantages are conferred by the fact that we are using this bead-based system means that we are able to multiplex different markers together and means we are able to extract extra information useful for pathologists.”

---PB--- PCR and multiplexing

Genera’s technology is based on its AmpaSand platform, modified silica beads that are coded with reference to size and colour intensity and are designed to be analysed by flow cytometry.

“We can code sub-clusters of beads within a group, and those sub-clusters can be individually identified by a flow cytometer,” Bollands says. “Those sub-clusters also have DNA markers on them that we can use to detect HPV and so forth.

“The key point for us is that the level of multiplexing we achieve is huge. Because we can code with reference for size and colour, the theoretical upper limit of our multiplexing ability is about 150 or 160, not withstanding all of the other variables that go into that.

“The other nice thing about the silica beads is that because they are extremely heat-resistant, we can put in fairly high stringency procedures, and that allows us to do very specific binding procedures.

“We have a particular piece of technology called enhanced solid phase PCR (ESP PCR), which allows us to do the PCR and the hybridisation of the beads in the same vessel. It shortens processing time and reduces the number of handling steps, and you can’t do that with latex beads, because they tend to gloop. That’s the very technical word we use.”

The company has also developed QPlots, a proprietary interpretive software for the interpretation of flow cytometry outputs. The software makes a call on each individual specimen, identifying whether it is high-risk HPV positive or negative, low-risk HPV positive or negative, such as for types 6 and 11, which cause can cause genital warts, or indeterminate. The whole test is carried out in a high-throughput, 96-well format.

“We can pretty much put any DNA marker onto our beads,” Bollands says. “We have some thoughts about how to extend our STD franchise, but I’m also personally quite interested in the pharmacogenetics side of things. We have started to explore some options looking at responsiveness to drugs and propensity of certain drugs to cause side-effects that are related to SNPs.”

Genera is commercialising molecular diagnostic products that sit in a sweet spot for corporate interest, he says. “It all has to be executed but the ideas are right. It is an interesting time and we are in the right space.”