Research foci Cell and Gene Therapy

The scientists of the Guest Research Group “Cell- and Gene Therapy” currently study cell- and gene based methods to correct hereditary liver diseases. Protocols have been developed to generate hepatocytes from gene corrected induced pluripotent stem (iPS) cells or through direct reprogramming methods. Transplantation of those cells requires clinically applicable liver repopulation methods, which allow controlled ablation of endogenous hepatocytes and expansion of transplanted cells. The researchers currently test several promising methods to achieve liver repopulation and definitive correction of disease phenotypes. Another approach focuses on direct in vivo genome editing of disease causing genes by CRISPR-CAS-9 based methods in combination with homologous recombination. The group has developed an “all in one” AAV based vector for in vivo correction of the liver phenotype in mice with hereditary tyrosinemia. For transient therapy of urea cycle defects we develop RNA based gene correction in combination with non-viral delivery systems.

Funding:

DFG OT131/6-1 and DFG OT131/6-2 

Publications

The research group currently studies feasibility of generating of chimeric livers in rats and pigs for organ transplantation in patients with endstage liver diseases. Blastocyst injection of iPS cells results in low grade chimerism in “offspring” animals with a high degree of iPS derived hepatocytes in the liver, if a cellular niche is provided. In a rat model chimeric livers will then be transplanted into a disparate host animal. They will study cellular adaption and immunological acceptance of the transplanted organ in the absence of immunosuppression. Pigs with a liver niche, which allows a high degree of hepatocellular chimerism, have been generated in cooperation with the Institut für Nutztiergenetik (FLI) in Mariensee. The generation of monkey / pig liver chimeras is planned as “proof of principle” studies for human applications.

Funding:

DFG-Koselleck: 131/7-1-3013879

Hepatocellular carcinoma (HCC) is the most common type of liver cancer. HCCs are largely unresponsive towards most existing therapeutics. There is thus an urgent need for the development of novel and more effective treatments. A class of small (~22 nucleotide) non-coding RNAs called microRNAs (miRNAs) is deregulated in a number of human cancers including HCCs. These miRNAs are emerging as promising therapeutic targets. Despite the enormous potential of miRNAs as therapeutics, the biological function of individual cancer-associated miRNAs is only just emerging. The group focuses on the identification of novel miRNAs involved in HCC to understand their function in HCC development and to determine their therapeutic potential in HCC.

Funding

Deutsche Krebshilfe 111147

Publications