Researchers from the National Centre of Competence in Research (NCCR), based at the University of Basel, together with Roche scientists have increased the sensitivity of array equipment to enable rapid analysis of gene activation.
Discovering which genes are activated by different treatments is a crucial stepping-stone towards personalised medicine. The publication of the entire human genome has prompted scientists to develop techniques to measure gene expression. However, gene activation changes from person to person. Treatments that are good for one person may not work on another or even do more harm than good. By analysing a person's genetic make-up, treatments can be tailored for each patient.
The NCCR scientists have developed new technology that can measure active genes directly. The sensors are made by attaching short nucleic acid segments to silicon cantilevers. Once activated, genes produce mRNA during transcription. This binds to the sensor causing it to bend and this physical change can be measured optically. The cantilevers are only 450 nm thick and therefore very sensitive.
Project leader of bio-nanomechanics Dr Martin Hegner told DrugResearcher.com that new technologies such as this one have struggled to succeed commercially in the past.
He said: "The market is heavily overloaded by traditional technology. The [new] technology is there but needs financial backing. It is quite a challenge."
Dr Hegner pointed out that in the past, researchers have concentrated on the physical side, for example making their devices user friendly, whereas his team have concentrated on perfecting the chemistry and biology used in the technology itself. The challenge facing scientists is to find the right nucleic acid segments to bind to specific genes rather than building the device itself. Dr Hagner hopes that with enough financial backing, their device could become available in as little as three to five years.
Roche already have experience marketing a product in this area with AmpliChip, the world's first microarray-based test approved for clinical use.
DNA microarrays are currently widely used to measure gene expression. However, extensive sample preparation is required, including labelling with a fluorescent or radioactive tag. This process is both time consuming and expensive. The machines can analyse over 4000 gene expression features and can be used to establish and validate new features. Real-time PCR can also used for the same purpose. Once this is achieved, a scaled-down, disease or treatment specific approach becomes more suitable. This is where the new nanomechnical sensors shine.
The new device is sensitive enough not to need a labelled sample, which leads to greater measurement precision. Results can be obtained in minutes and so the technique can monitor biological processes in real-time. As such, the new technology is envisioned to work along side existing methods to one day provide clinicians with a user friendly and fast method of analysing therapy response. If the amount of functional product or the timing of gene activation is altered, it can cause disease. Therefore, the nanomechanical sensors can also be used to assess disease risk and progression. The technology isn't just restricted to genes though. The nanomechanical sensor is also being used by Dr Hagner's group to examine microorganisms and both membrane and soluble proteins.
Dr Hagner said: "It is a really versatile tool which lets us work across disciplines within one research group."