Experimental Therapies for Inherited Metabolic Liver Disease

The CCMT Lecture Series, sponsored by The Raymond G. Perelman Center for Cellular and Molecular Therapeutics at CHOP, presents:

Experimental Therapies for Inherited Metabolic Liver Disease

Speaker:
Karl-Dimiter Bissig, MD, PhD

Associate Professor of Pediatrics
Alice Chen Pediatric Genetics and Genomics Research Center
Duke University School of Medicine

Host:
Valder Arruda, MD, PhD

Please email arruda@email.chop.edu if you would like to meet with the speaker.

About the topic We recently developed a new therapeutic concept called metabolic pathway reprogramming, which couples the power of CRISPR/Cas9 technology with a strategy from pharmacology, namely, to inhibit an enzymatic pathway rather than directly edit a disease-causing gene.  We demonstrate the efficacy of this approach by using CRISPR/Cas9 to convert fatal type I tyrosinemia into benign type III tyrosinemia in mice^1^. In contrast to small molecule drugs, genome editing is sequence specific and neither its therapeutic potential nor its side effects can be evaluated properly in conventional animal models. To this end, we developed novel xenograft models for metabolic liver disease, which should allow us to properly validate this therapy in the context of primary human cells. We will present the xenograft platform and ongoing research applying metabolic pathway reprograming in vivo.