Improving the Performance of Standard Reporter Assays

Marco Leu, Genestream Pty Ltd.

How was GeneStream set up?

GeneStream was founded by Dr. John Daly of Perth in Western Australia. After graduating in molecular biology at the University of Western Australia, he worked for several years in academic science. He then went to Europe where he stayed for about 5 years and worked for pharmaceutical companies like Novartis.

John then went back to Perth and completed another Post Doc at the University of Western Australia. John had dealt a lot with cell-based reporter assays, noticing their limitations; namely that they didn't show enough sensitivity to activation or inhibition of transcription. Consequently, he came up with an idea to improve the performance of standard reporters so that they would respond a lot faster to any intracellular event that affects transcription. This concept, now marketed under the trade mark RapidReporter, marks the starting point of GeneStream.

What would you say are the main advantages of this enhanced reporter assay compared to the competition?

The most important difference to a standard reporter is certainly that the RapidReporter responds a lot faster and a lot more accurately to whatever activates or inactivates transcription. It therefore provides a much higher sensitivity to any cellular event that leads to altered transcription.

For example, if we take cells expressing a standard reporter, for example a luciferase, and then treat the cells with a drug that totally blocks its transcription, then it still takes about 16-18 hrs for the luciferase signal to drop to 50% of its initial levels. We call this the "effective half-life" and for some reporters (like fluorescent proteins), it can be even worse.

In contrast, the RapidReporter versions of those same reporters show effective half-lives of only 1.5 hrs. We have also used the RapidReporter in miniaturized drug screening experiments where the improved responsiveness results in a substantially enhanced difference between the signal of active vs. inactive compounds as compared to a standard reporter. Therefore, the RapidReporter dramatically facilitates the identification of active compounds, which results at the end in a lot less false negatives, but also a lot less false positives of course.

Taking a standard high throughput screening (HTS) assay, you often measure each sample just once. So you basically only have one shot per compound. If that signal is not really substantially different from an inactive or control sample you will most likely miss it. Using the RapidReporter in a similar HTS set up will considerably facilitate the distinction between active and inactive compounds. You should therefore be able to identify a lot more positive leads.

Which customers do you have for these new assays?

We are targeting mainly pharmaceutical companies that perform HTS in-house, and also companies that provide screening services. Of course, the RapidReporter system is not restricted to HTS. It can basically be used in any cell-based assay in which you are after a really sensitive method to detect changes in reporter signal.

Who is using it at the moment?

The company was founded in 2001, so we are really just at the very beginning of our marketing phase. We are looking for anyone willing to test our system in their own drug screening applications. Of course, we are also trying to get our foot in the door of pharmaceutical companies to convince them of the quality of our product.

Do you think it is a disadvantage being based in Australia?

It can require some long distance travel to make the personal contacts. However, nowadays with the Internet and easy international communication, it is becoming a lot less trouble I think. Distances don't really matter that much any more.

The Australian government has put a lot of money into biotechnology, so I think it is actually an interesting place to be right now. Biotechnology looks like becoming an important technology for Australia and it's quite fascinating to be part of that initial wave. And of course, Perth and Australia offer a lot more than just science!

Further Information: http://www.genestream.com.au