Comparing epitope preferences of full length and single domain antibodies

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This project will compare structural features of the binding sites of full-length antibodies and single-domain antibodies. The majority of antibody therapeutics are monoclonal antibodies (mABs), comprising the entire Ig molecule. Despite their success as therapeutics, the high molecular weight of mABs can cause challenges during production and can lead to reduced tissue penetration. Due to the presence of the fragment crystallisable region in mABs, they can also be overly immunogenic in patients. This has led to an increasing interest in single domain antibodies, and their derivatives. Single domain and full length antibodies have different biophysical characteristics and are considered therapeutically useful in different contexts. So far only one single domain antibody has been approved for clinical use but an increasing number are appearing in clinical trials. The purpose of this project is to leverage available data on binder- target pairs, and to use this information to predict whether a single domain, or full length antibody will effectively target a given epitope. This information will allow us to select the appropriate molecule format when working on new protein targets within discovery campaigns. Ultimately, this will give us the best chance of maximising the therapeutic effect of a potential drug candidate, and thereby increase its chances of reaching the clinic. This project falls within the EPSRC 'chemical biology and biological chemistry' research area and will involve collaboration with biotechnology company Twist Bioscience.