Oregon Health & Science University

Dana-farber-cancer Institute Inc.

Mayo Foundation for Medical Education and Research

Leland Stanford Junior University

Markus Grompe

Alan D D'Andrea

Philip R Streeter

Craig Dorrell

Kelsea M Shoop

Stephanie L Abraham

Scott Nyberg

Joseph Lillegard

Raymond Hickey

Mark A Kay

David T Weaver

Toshiyasu Taniguchi

Edward A Fox

Richard Kennedy

Cynthia Timmers

Willscott Naugler

Hisaya Azuma

Muhsen Al-Dhalimy

The present invention provides methods of increasing the efficiency of genome editing.

Methods for enhancing the efficiency of gene editing

This present invention compositions and methods of treating cancer and methods of accessing/monitoring the responsiveness of a cancer cell to a therapeutic compound.

Treating cancer deficient in FANCA, FANCD2, FANCE, or FANCG with an ATM inhibitor

Methods of normalizing bile acid production in a mouse engrafted with human hepatocytes by the administration of human FGF19 are disclosed. Also disclosed is a transgenic host animal, such as a mouse, that expresses human FGF19 that has normalized bile acid production when engrafted with human hepatocytes.

Normalization of the enterohepatic circulation in animals with a chimeric humanized liver

Described herein is the generation of Fahheterozygote pigs by homologous recombination and somatic cell nuclear transfer, and a method for producing Fahhomozygote pigs. The Fah-deficient pigs of the disclosure can be used for a variety of research and therapeutic purposes, such as for the expansion of human hepatocytes, and as large animal models of hereditary tyrosinemia type 1, cirrhosis and hepatocellular carcinoma.

Fumarylacetoacetate hydrolase (Fah)-deficient pigs and uses thereof

Methods and compositions for the diagnosis of cancer susceptibilities, defective DNA repair mechanisms and treatments thereof are provided. Among sequences provided here, the FANCD2 gene has been identified, and probes and primers are provided for screening patients in genetic-based tests and for diagnosing Fanconi Anemia and cancer. The FANCD2 gene can be targeted in vivo for preparing experimental mouse models for use in screening new therapeutic agents for treating conditions involving defective DNA repair. The FANCD2 polypeptide has been sequenced and has been shown to exist in two isoforms identified as FANCD2-S and the monoubiquinated FANCD-L form. Antibodies including polyclonal and monoclonal antibodies have been prepared that distinguish the two isoforms and have been used in diagnostic tests to determine whether a subject has an intact Fanconi Anemia/BRCA pathway.

Methods and compositions for the diagnosis of cancer susceptibilities and defective DNA repair mechanisms and treatment thereof

Fumarylacetoacetate hydrolase (fah)-deficient pigs and uses thereof

Described herein is a method of expanding human hepatocytes in vivo using an immunodeficient mouse which is further deficient in fumarylacetoacetate hydrolase (Fah). The method comprises transplanting human hepatocytes into the immunodeficient and Fah-deficient mice, allowing the hepatocytes to expand and collecting the expanded human hepatocytes. The method also allows serial transplantation of the human hepatocytes into secondary, tertiary, quaternary or additional mice. Also provided are mutant mice comprising homozygous deletions or point mutations in the Fah, Rag2 and Il2rg genes.

Method of expanding human hepatocytes in vivo

Isolated monoclonal antibodies are disclosed herein that specifically bind a cell surface antigen expressed on the human pancreatic endocrine cells or a subset thereof, and/or a precursor thereof. Isolated monoclonal antibodies are also disclosed herein that specifically bind a cell surface antigen expressed on human pancreatic exocrine cells or human ductal cells. Humanized forms of these antibodies, and functional fragments of these antibodies, are also disclosed. The antibodies can be conjugated to an effector molecule, or a detectable marker. These antibodies are of use to detect and/or isolate pancreatic cells or a subset thereof. Methods of treating a pancreatic tumor are also disclosed.

Monoclonal antibodies and their use

Isolated monoclonal antibodies are disclosed herein that specifically bind a cell surface antigen expressed on the human pancreatic endocrine cells or a subset thereof, and/or a precursor thereof. Isolated monoclonal antibodies are also disclosed herein that specifically bind a cell surface antigen expressed on human pancreatic exocrine cells or human ductal cells. Humanized forms of these antibodies, and functional fragments of these antibodies, are also disclosed. The antibodies can be conjugated to an effector molecule, such as a detectable marker, a therapeutic agent, or a toxin. These antibodies are of use to detect and isolate pancreatic cells or a subset thereof. The antibodies can be used for in vitro or in vivo detection and/or isolation of pancreatic endocrine cells. Methods of treating a pancreatic tumor are also disclosed. In several examples, the isolated monoclonal antibodies bind pancreatic endocrine cells and can be used to detect diabetes or a pancreatic endocrine cell tumor.

This invention provides a method of regenerating a functional liver by transplantation of pancreas cells. Also provided are pancreas cell capable of regenerating functional liver tissue.

Growing community of inventors

Portland, OR, United States of America

Markus Grompe