Mapping out the future of drug discovery via gene expression analysis

© From left to right: Marine Vallez, Daniel Alpern, Riccardo Dainese, Pierre Yves Helleboid, Mustafa Demir, Bart Deplancke and Fiona Joseph. Photo by Marjan Biocanin

© From left to right: Marine Vallez, Daniel Alpern, Riccardo Dainese, Pierre Yves Helleboid, Mustafa Demir, Bart Deplancke and Fiona Joseph. Photo by Marjan Biocanin

Developing a new drug is a lengthy and costly process. Daniel Alpern, Bart Deplancke, and Riccardo Dainese have developed a new technology - MERCURIUS - which offers a quick and cost-efficient way to analyse multiple gene expressions. These Innogrant winners discuss how their cutting-edge approach will help bring essential therapy to patients sooner. 

The road to developing a new drug is a long and arduous one. Of the 10,000 different compounds that may start the drug discovery process, 250 of them might get to pre-clinical development. Five will reach clinical trials. Only one is likely to make it all the way through the pipeline and be approved for use. 

Each year, over 60,000 new clinical trials start. On average, the Food and Drug Administration (FDA) only approves around 45 new drugs for use. This process doesn’t come cheaply. According to research from the London School of Economics, the average cost of developing a new drug is $1.3b[1].

What if there was a way to make this drug development process quicker, cheaper, and more efficient?

Alithea Genomics, a new venture out of EPFL and co-founded by Daniel Alpern, Bart Deplancke, and Riccardo Dainese, think they may have the answer. We spoke to them about their new technology, MERCURIUS, and what it may mean for drug development in the future.

How did Alithea Genomics start? 

First a little background… In almost every human cell, there is a chemical called DNA. DNA contains instructions – known as genes - which tell the cell how to make molecules called mRNAs. These mRNAs are used by the cell to generate proteins. While there are around 20,000 genes in each cell, only a number of them will be active (i.e. expressed or produce mRNAs) at any one time, depending on the type of cell. By measuring the expression of these genes in terms of the number of mRNAs, we can understand a lot about the cells – everything from the underlying cause of a disease or how the cells react on different treatments. 

At the Insitute of Bioingeneering at EPFL we were conducting a project aimed at understanding how genetic differences between humans can affect their susceptibility to different diseases. This project required analyzing the expression of over 20,000 individual genes in a large set of tissue samples. That’s a lot of genes and analyses! We considered different methods to do this work but these methods were either not suitable to analyse that many genes, or very long to perform and very expensive. 

We wanted to simplify this process. We put together available protocols and optimized them for what we wanted to do. In the end, we came up with an approach allowing us to perform gene expression analysis in a way that was quicker and cheaper, but just as effective. Soon, other laboratories were approaching us to support them on their large-scale gene expression analysis projects and it just grew from there. We realised we had developed a technology that could help labs analyse thousands of genes for hundreds of samples at once (rather than one gene at a time) – significantly reducing costs and speeding up the process. MERCURIUS and Alithea Genomics were born!

How does the technology work?

To measure the activity of a gene, we need to measure its mRNA. This isn’t an easy process! While there are a number of methods to do this, the most of them starts with transforming the mRNA into DNA. Once you’ve done this, we use a routine assay called PCR (Polymerase Chain Reaction). This method makes billions of copies of the DNA so you have a large enough sample to study it in detail. While PCR only allows you to study up to about 5-10 different genes it is the one mostly used for research, diagnostics and drug discovery by pharmaceutical companies at the moment. In fact, PCR is how COVID-19 is currently being detected in millions of samples in laboratories across the globe.

Cutting-edge technologies are now paving the way for new genetic testing. One of these new approaches is called RNA sequencing. It allows researchers to reliably identify and measure the activity of all of the genes in a sample. The main problem with RNA sequencing is the work and investment involved – it’s a time-consuming process with large associated costs. 

That’s where where our technology comes in…

How might the technology be used?

At the moment, our technology is best suited for research laboratories in academia or industry who are interested in analysing many samples at once. For example, a lab comparing healthy samples with disesased samples. There’s also huge potential to support large projects in industry – such as those conducted by pharma, biotech or agricultural companies. 

Outside of academia, sample testing is still done using fairly old, low throughput technologies. For example, in the pharmaceutical world, when they’re doing drug development testing, the process they use only allows them to assess the efficacy or toxicity of a drug on maybe a handful of genes, 10 or so. They introduce their potential drugs to the samples and they measure the activity of these genes using PCR or other basic methods. They can then make an assessment on whether the drug has the potential to produce the desired outcome or not. 

Why do they work this way when there’s so much great technology out there? Surely their assessments would be better informed if they could analyse the entire set of genes? The main reason is cost. Pharmaceutical companies do millions of tests a year. The price of current RNA-sequencing analysis solutions on the market is still too high for it to be cost-effective for such a large number of tests. With our new technology, MERCURIUS, we hope to allow the industry to analyse 100 times the number of genes, up to four times as quickly, for around the same price as they’re currently paying.

How is MERCURIUS used in the lab? 

Say a lab technician has 100 RNA samples. Normally, each sample has to be processed individually, following a two to three day protocol to prepare it for sequencing analysis. However, by using our MERCURIUS kit, they can perform a simple enzymatic reaction to label their RNA. Once that’s done, they take all their samples and put them into one test tube.

From this point, all the remaining processes are performed in a one tube in a single day. Our technology will then generate the information for each individual sample from the raw sequencing data. Our method dramatically reduces the time and cost of sample preparation for sequencing. 

Through the MERCURIUS kit, researchers can perform RNA-sequencing at a price comparable to routine PCR testing. For a pharmaceutical company, this has great potential benefits – instead of testing the efficacy of a drug on a handful of genes, they will be able to quantify all the genes in the sample. They will then have the data which allows them to make well informed decisions on the drug early in the pipeline – saving money and time - and bringing much-needed therapies to patients sooner. 

Theres obviously lots of potential, so whats next? How will the Innogrant help you?

At the moment, MERCURIUS can meet the needs of research labs in the academic world but we want to expand our reach – providing support for biobanks to make use of their valuable data and for pharmaceutical industry to accelerate their drug screening tasks. 

For this, we need to evolve our products, enabling higher-level testing capacity and automation. The Innogrant is going to allow us to take our technology one step further and adapt our offering to industrial standards. We know there’s an opportunity to make our process even more efficient - providing a kit for profiling even more samples at once and allowing to bypass tedious RNA extraction step. We want to thank EPFL and all our other funders for their support. This is an exciting time for us and the future looks bright!

[1] https://www.biopharmadive.com/news/new-drug-cost-research-development-market-jama-study/573381/

References

Alithea is based in EPFL’s Laboratory of Systems Biology and Genetics under the supervision of co-founder, Professor Bart Deplancke. Find out more on their website

For more information on Innogrants and details on how to apply, visit the Startup Unit website.


Author: Imogen Hitchcock
Source: Innovation