Technologies for chemical engineering of targeting protein therapeutics

The aim of the proposed project is to explore new concepts for chemical engineering of protein therapeutics in order to improve the efficacy and reduce the side effects.

The first part of the project concerns bispecific targeting using affinity reagents linked by peptide nucleic acid (PNA) hybridization.

The purpose of bispecific targeting is to increase the selectivity for the targeted cell type, such as a tumor cell having an abnormal expression of surface receptors, and give new opportunities for individualized treatment. The second part of the project is focused on delivery of cytotoxic payloads through a pretargeting system.

An earlier developed pretargeting strategy based on PNA hybridization will be further investigated by design and synthesis of probes with substituted, hydrophilic building blocks and conjugation to charged polymers to improve the biophysical properties of the drug-PNA conjugates.

The third part of the project explores light-controlled activation of targeting proteins to increase the selectivity for the targeted tissue, which is a novel concept inspired by recent progress in photopharmacology. The project will focus on design, synthesis and in vitro evaluation of new constructs.

The overall aims of the project are to identify and develop new formats for protein therapeutics, which will expand the repertoire of druggable targets and increase the stringency of the targeted therapy.