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Research Strategies


Drugs that contain nitisinone, a synthetic inhibitor of tyrosine metabolism, are widely used as a standard treatment of HTI, along with dietary restriction of tyrosine. Although these treatments effectively lessen the effects of HTI, they are not curative. Researchers at the Li Weibo Institute for Rare Diseases Research are conducting studies that could potentially lead to curative gene therapies for HTI patients. Specifically, the Xue, Gao, and Sontheimer labs have developed novel genome-editing strategies that aim to correct a broad range of genetic disease mutations, including those in HTI. They have used these strategies in mouse models of HTI to successfully correct FAH mutations, rescue the disease phenotype, and reprogram the tyrosine degradation pathway. Their research findings demonstrate the effectiveness of genome-editing strategies in animal models of HTI and the potential for their use as a therapeutic strategy in human patients.


Cas9-mediated allelic exchange repairs compound heterozygous recessive mutations in mice

Authors: Wang D, Li J, Song CQ, Tran K, Mou H, Wu PH, Tai PWL, Mendonca CA, Ren L, Wang BY, Su Q, Gessler DJ, Zamore PD, Xue W, and Gao G

Published in 2018 in Nature Biotechology

Cas9-mediated gene editing promises to correct DNA mutations underlying human diseases. However, monogenic recessive genetic diseases typically involve many distinct mutations present across the gene. For example, more than 95 known mutations in the FAH gene can cause HT1. Consequently, the rapid development of gene editing as a human therapy requires a mutation-independent gene repair strategy. This study presents such a genome-editing strategy that corrects compound heterozygous mutations and rescues the disease phenotype in mouse models of HTI. This strategy has the potential to treat a large population of patients bearing different mutations of each disease-gene allele.


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Hereditary Tyrosinemia Type I Investigator

Guangping Gao, Ph.D.

Guangping Gao, PhD

Co-Director, Li Weibo Institute for Rare Diseases Research, Director, Horae Gene Therapy Center and Viral Vector Core, Professor of microbiology and physiological systems, Penelope Booth Rockwell Professor in biomedical Research

Gao Lab

Erik Sontheimer, PhD

Erik Sontheimer, PhD

Professor, RNA Therapeutics Institute

Sontheimer Lab

Wen Xue, PhD

Wen Xue, PhD

Assistant professor of RNA therapeutics

Xue Lab

Clinical Trials

At the Li Weibo Institute for Rare Diseases Research, our researchers and clinicians are dedicated to finding new treatment options for patients. Our clinical trials program is another way we continue to advance treatments and make new discoveries. If you or someone you know may be interested in a clinical trial, please subscribe for updates and you will be notified when we open up a new trial.