Non-viral gene delivery

In the last few years, gene-therapy has focused the attention of the scientific community since it could be an efficient new way to cure several major human diseases such as cancer, AIDS, cystic fibrosis, anaemia or progeria. The concept of gene therapy is the substitution in the cell nucleus of abnormal genes causing diseases by normal healthy DNA sequences. The main challenge in gene therapy is the design of specific carriers, which allow efficient delivery of the healthy genes in the cell (transfection). Such carriers should be able to transport DNA in the bloodstream, to cross efficiently cell membranes and to free the genetic material near the cell nucleus.

Typically, viral systems are the most effective carriers for gene delivery. Viral systems can selectively target cells and usually possess a very high transfection efficiency, leading to high gene expression rates. However, viral carriers can also be very toxic for the human body. Moreover, their isolation from biological sources and their processing are very expensive. Therefore, non-viral gene carriers such as synthetic polymers, proteins or liposomes are more and more investigated for gene therapy. In particular, synthetic polymers are very attractive, as compared to biopolymers, since they can be produced in high quantity for relatively low costs. Moreover, their chemical structure can be precisely adjusted for optimal properties.

The goal of this project is to study the synthesis, characterization and clinical applications of new non-viral polymer gene carriers based on cationic polymers such as polyethyleneimine (PEI) or poly(vinyl amine). Such polycations form soluble complexes with DNA in aqueous solution, and therefore allow to transfer genetic materials inside cells. The chemical modification of the raw polymer (modification with specific cell-targeting ligands or water soluble polymers) allows an improved transfection efficiency, gene expression as well as a reduction of the cytotoxicity. Both synthesis and characterization are investigated in our research group at Fraunhofer IAP and MPI. The in vivo an in vitro experiments (Luciferase and Bradford assays) are investigated at the technical university of Munich and at the Robert Koch institute in Berlin.