Genomics and technology- Optimising drug discovery

11 April 2016

We recently talked to Dr Michael Wilson from CSL Limited to learn how genomics is opening the way for more targeted and effective individual treatments.

After working in academia in the UK for more than five years, Dr Michael Wilson joined GlaxoSmithKline as his first venture into the pharmaceutical industry which aligned well with his ongoing interest in translational science. “I wanted to work on things that were going to go into clinical trials and see the tangible side of things”, says Dr Wilson. It is his interest in translational science that resulted in the shift from academia to industry, and essentially led Dr Wilson to work on a range of projects that can potentially go to market and make a tangible difference to a patient’s life.

Today, Dr Wilson heads up the Molecular Biology group at CSL. An experienced pharmaceutical professional, he has successfully developed and led drug development project teams for a range of disease indications including inflammatory conditions, airway disease and oncology.

Genomics and clinical medicine

Knowledge of all the human genes and their functions optimises the drug research strategy and drug discovery development processes. The potential implication of genomics in clinical research and clinical medicine is that disease could be treated according to individual genetic markers, selecting medications and dosages that are optimised for individual patients. The power of gene sequencing and analysis means we are able to define patient populations genetically to improve outcomes by predicting individual responses to drugs. “Gene expression analysis gives us better insights into how drug candidates could be working in a particular disease. Comparing the expression profiles of normal individuals with diseased patients helps us drill down to determine whether the molecular pathways which the drug affects are potentially involved in the disease”, explains Dr Wilson. “The diseases we work with are often very heterogeneous – diseases such as rheumatoid arthritis and asthma are generic names for diseases that can be driven by a range of biochemical mechanisms. Therefore, it is well established that some patients respond to a given treatment regimen better than others.” “What we are trying to understand is if there is a subset of patients which could potentially benefit by treatment with our particular drug candidate. Access to high quality gene expression data enables better decision making in the drug development process, because it potentially allows us to identify patients where our drug candidates could have greater efficacy”, explains Dr Wilson.

New technologies, new avenues

Genetic information has immensely helped researchers understand the mechanisms of disease as well as individual patients’ reactions to medications. Warfarin is an example of pharmaceuticals that either utilise genetic information to inform dosing, or whose activity and effectiveness is determined by inherent genetic properties of the patient. This genetic information is a result of achievements using technological advances. New technologies open new avenues of development, and for CSL they help identify new drug targets to pursue. Dr Wilson and his team recently worked with AGRF to understand antibody repertoire through sequencing analysis.

“A lot of therapeutics are antibody based. Understanding the antibody repertoire at a sequence level saves a lot of time and improves quality in our experimental design. The technology impact is read length, which has become significantly longer over the past few years. The antibody region that is variable and binds to the target antigen is about 450 base pairs in length. This technology improvement allows us to sequence the whole region in one hit”. “We can now complete a full antibody repertoire analysis which is a key technological gain for us”. “Other key technological shifts that will really make an impact include genomic sequencing for gene insertion analysis and genome wide association SNP analysis”.

Accessing genomic technology

Outsourcing services is a strategic decision for most organisations. In particular when technology changes rapidly and requires frequent cycles of new capital expenditure. This was the key driver for Dr Wilson’s group to outsource genomic services. “It’s vital to work with an organisation that has a strong background in technology. It becomes even more important when you start exploring a new area or developing methodologies”, said Dr Wilson.

Working with Dr Wilson and the CSL team on RNA sequencing analysis, a collaborative approach with AGRF helped them transition methodologies from microarray to RNA sequencing. A project that required regular communication and a great deal of advice. “It becomes more than just receiving data. It is the expertise that comes with it. For us it is most important that we work with people we trust”, says Dr Wilson. “Having easy access to a genomics provider was a key factor in our decision making. Having access to high quality sequencing and capability just around the corner is something we really value”.