Engineering of single-domain antibodies
Rapid current developments in protein structure prediction, protein engineering, and protein design allow novel in silico approaches that were not feasible until recently as exemplified by the 2024 Nobel prize in chemistry. Moreover, novel DNA synthesis approaches allow rational design of tailored variant libraries which can be used to generate large amounts of VHH variants based on a lead sequence.
At QVQ, we can leverage our extensive experience in sdAb development, access to a wet lab, and phage display setup to suggest, produce and experimentally test in silico engineered sdAbs and/or sdAb libraries.
For example, we can use protein engineering to insert protein A binding affinity or to enhance the intrinsic enzymatic- and thermostability. QVQ can experimentally validate improved thermal stability by Thermal Shift Assays (TSA) or Differential Scanning Fluorimetry (DSF).
Another common request is to enhance the binding affinity of a sdAb (a.k.a. affinity maturation). Both experimental and in silico engineering approaches can be used in isolation or combined to rationally introduce mutations to improve the binding affinity.
The most requested (in silico) protein engineering approaches are humanization and increasing developability. We offer bespoke solutions for your project and provide a realistic picture of what engineering approaches are available and could be applied by QVQ for sdAb improvement.
