PsoBiBi – Development of psoriasis therapeutics using bicyclic genetically encoded libraries

The incurable, inflammatory skin disease psoriasis affects 2 percent of the world's population. Therapies have significant side effects such as systemic weakening of the immune system or limited patient response. Toll‑like receptors (TLR) of the innate immune system play a key role in inflammatory skin diseases. For example, keratinocytes show increased TLR expression in psoriasis. In the Psobibi project, TLR antagonists for topical application are identified, synthesized and validated as an alternative to systemic psoriasis treatment.

Screening of libraries requires the individual testing of substances. In this project, a genetically encoded fragment‑based platform technology from the company 48Hour Discovery is used for screening for peptides that bind to multiple TLRs. These phage libraries comprise more than 109 linear and cyclic peptides, which are screened simultaneously and in competition to each other via cell‑based TLR reporter gene assay (EP 2 041 172) and via a cell‑free system at Fraunhofer IGB. Thus, TLR‑binding peptides can be found in just one procedure and identified by phage coding using deep sequencing.

Hit peptides are provided by EMC microcollections GmbH and their antagonistic effect is validated at the IGB via the cell‑based reporter gene assay. These antagonists will be investigated with human 3D in‑vitro skin models complemented by TLR overexpressing reporter gene skin cells (EP 2795318A1) and psoriasis biopsies in topical application.