Improved Drug Target Characterisation and Screening - Isis Project No 3579

A new method for isolating and manipulating transmembrane protein drug targets through control of their membrane environment; allows for better target characterisation and more predictive nanoarray screening data.

Marketing Opportunity

This technology will appeal to pharmaceutical and biotech companies conducting transmembrane protein research into therapeutics and diagnostics due to its ability to closely model these proteins’ behaviour through being held in the correct lipid environment.

The Oxford Invention

It is estimated that around 70% of drugs in development target transmembrane proteins. To retain full functionality, these proteins typically must be held in the membrane environment that they would do in vivo: they should sit within a lipid bilayer membrane of the right thickness and molecular composition. It is known that when transmembrane proteins are placed in membranes too thick or thin, they can aggregate together or change shape, both of which cause loss of functionality. Furthermore, current methods of screening proteins rely on immobilising purified proteins on substrates in the absence of any bilayer, yielding data of questionable utility.

This technology offers a method by which proteins’ preferred membrane thickness can be readily identified by presenting them with membranes of differing thicknesses and composition (‘hydrophobic matching’). It also provides the possibility to observe single targets at the molecular level or to screen targets held in proteoliposomes, organised into protein nanoarrays. Further possibilities include:

• Mimicking the natural process of protein trafficking by lipid raft control;
• Use with or without cholesterol;
• Fine tuning of target density within the membrane or lipid raft;
• Improved characterisation of targets and consequently more predictive data sets.

Atomic force microscopy images of a membrane of two different thickness domains; the target protein resides in the thicker region due to hydrophobic matching.

Patent Status

The invention is the subject of a US patent application and a scientific publication. Isis would like to talk to companies interested in developing the commercial opportunity.

Request Further Information: Project Number 3579 - Improved Drug Target Characterisation and Screening