Characterisation of antibodies and affinity reagents to promote the adoption of robust and reproducible non-animal reagents

Harvinder will collaborate with nine research groups at the Universities of Leicester and Nottingham to characterise affimers as alternatives to animal-derived antibodies. He will also work with manufacturing partners to replace commercially available animal-derived antibodies in their catalogues with non-animal alternatives where they are shown to offer improved specificity and performance.

This award was made as part of the 2024 non-animal derived product validation grants supported with funding from the Department for Science, Innovation and Technology (DSIT).

Affinity reagents such as antibodies are used in most biomedical research labs to study proteins. Currently, the most used affinity reagents are animal-derived polyclonal and monoclonal antibodies. Our research has shown that animal derived antibodies are more likely to fail quality control (characterisation) experiments than recombinant antibodies, which can be produced using non-animal methods. The wider use of recombinant antibodies would not only reduce and replace the use of animals used in production, but also reduce animal use through the generation of data that is more reliable and reproducible.

We are already promoting the adoption of high-quality affinity reagents that do not rely on animal-based technologies through the Open Science partnerships, YCharOS and the Only Good Antibodies(OGA) community, including 80% of global recombinant antibody manufacturing. Our work is leading to the removal of mainly low-quality animal-derived polyclonal reagents from the market (~20% of those tested).

But many poor-quality antibodies are still used in research, with end-user focus groups highlighting the critical need for trusted characterisation data. This project will, together with our current MRC Better Methods award, allow for the characterisation of ~150 antibodies and affinity reagents against 15 targets.

These targets are selected because of:

• High community needs for robust reagents to study these targets
• The availability of non-animal affinity reagents or recombinant antibodies from our partners
• The high feasibility of knockout studies
• A commitment from 9 research groups to use these reagents within their funded research projects

We will use our standardised industry-endorsed genetic knockout strategies that are trusted by our partners, and result in changes to their catalogues. Based on our previous work this would result in the potential reduction and replacement of ~96 animal-derived reagents relying on ~290 mice and rabbits (mainly). We will accelerate the 3R impact of our studies by working with local researchers, who have committed to using our data, to select their affinity reagents. This will also include working with us to understand the scientific and 3R advantages of non-animal affinity reagents. The wider adoption of these reagents will be promoted by our funded OGA outreach.

This project will increase confidence in non-animal affinity reagents and ensure that research funding is used to produce trustworthy and replicable data. As a result, the discovery of novel biomarkers for cardiovascular disease, studies of airway inflammation phenotypes, and mechanisms of lung fibrotic diseases, will become more robust and impactful.