The research of our group is focused on three complementary axes that aim to enable the development of biomedical applications using new modified proteins:
1-Design of novel proteins for diagnostic and therapeutic interventions
The creation of novel molecules capable of specifically recognising a biomarker associated with a disease is essential for the development of biomedical applications, whether for diagnosis or therapy. We exploit a wide range of skills in molecular biology, protein biochemistry, cell culture and microbiology to develop targeting proteins. We focus on tumour and infectious pathological contexts that often require similar approaches to engineer targeting proteins. For this purpose, we use antibody fragments (VHH, scFv, F(ab’)2) and our Affitins that we can generate against any type of target. In order to create optimal targeting proteins, we are building new formats that can combine several of these types of affinity proteins.
2-Protein engineering for improving targeting
The creation of new targeting proteins often involves the development of new formats related to multivalence and multispecificity. One of our objectives is to better understand the influence of the manner of linking recognition units (nature, length of spacers), valency, and affinity in order to define principles for the design of optimal proteins of biomedical interest.
3-Development of Affitins
We have invented and developed Affitins as a novel class of binding proteins. Affitins are derived from Sul7d proteins found in archaeal extremophiles such as Sulfolobus acidocaldarius, Sulfolobus solfataricus, or Acidanus hospitalis which optimally grow at pH 2-3 and temperatures of 75-80 °C. Using combinatorial engineering against protein or bacterial targets, we have generated a number of Affitins which show specificity and affinity for their targets in nanomolar and subnanomolar ranges. Affitins are small (7 kDa), highly thermostable (up to 90°C), pH-stable (from 0 up to 13), highly soluble, well-produced in Escherichia coli grown in flasks (up to 200 mg/L culture) and can be easily engineered. Furthermore, we have shown that Affitins are well-suited for detection, capture and inhibition applications for which protocols can require harsh conditions of pH, temperature or a dry condition. In addition, Affitins are weakly or non-immunogenic, stable in serum and do not accumulate in untargeted organs in mice. All these favourable properties make them attractive molecules for biomedical applications. Selections of Affitins are performed using ribosome display, one of the most powerful in vitro selection techniques.