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Genome Engineering & iPSC Center Core

基因组工程

基本信息

批准号：
10630356
负责人：
JEFFREY D MILBRANDT
金额：
$ 15.35万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-24 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10630356
关键词：
Alleles Animal Model Animals Back Biology Biopsy CRISPR/Cas technology Cell Line Cells Consultations Dedications Derivation procedure Development Disease Disease Pathway Disease Progression Dissection Ensure Epithelial Cells Epithelium Epitopes Equipment Evaluation Fibroblasts Generations Genetic Genetic Diseases Genome Genome engineering Goals Growth Guide RNA Hela Cells Human Resources Individual Infrastructure Instruction Kidney Laboratories Lead Liver Fibrosis Maintenance Mutation Organism Pathway interactions Patients Plasmids Pluripotent Stem Cells Production Proteins Reagent Research Research Personnel Research Support Sampling Science Scientist Services Skin System Techniques Technology Tubular formation Universities Urine Validation Variant Washington Work clinical application design drug development experimental study functional genomics gene replacement genome editing implementation facilitation induced pluripotent stem cell induced pluripotent stem cell technology knockout gene mutant new technology novel strategies novel therapeutics programs repaired service utilization stem cell technology stem cells success

项目摘要

Project Summary Genome engineering and patient-derived pluripotent stem cell technology have dramatically changed our abilities to understand disease pathways. These two technologies are recent additions to our investigative armamentarium but have rapidly permeated all aspects of biomedical science, providing unprecedented power to discover how perturbations of components in specific pathways lead to disease. The Genome Engineering Core C is composed of 11 investigators and all of the necessary equipment, reagents and expertise required to perform the experiments needed to support the research goals of the 3 projects outlined in this PO1 renewal application entitled “New therapies for liver fibrosis and hyperproliferation in alpha1-AT deficiency (ATD)”. Our facility is housed within the Washington University Genome Engineering and IPSC Center (GEiC) and was established and is overseen by the Department of Genetics. It was created to facilitate the implementation of these powerful new technologies in laboratories at Washington University. All projects proposed within this PO1 renewal application plan to extensively utilize the services provided by the Core. These experiments are largely aimed at the ongoing evaluation of modifying variants in ATD and their potential exploitation for development of new treatments for this disorder. The services to be utilized include the design, construction and validation of genome editing reagents (e.g. gRNAs, donor plasmids, and Cas9 derivatives). The Core also produces modified cell lines using genome editing technologies, including gene knockout, variant introduction, epitope tagging or gene replacement. These cell lines will be used to better understand the biology of ATD and to assess the impact of variants selected for their potential to modify disease progression and facilitate drug development. The Core will also design and generate materials needed for rapid production of animal models harboring selected variants. The Core produces iPSCs from both skin biopsies and the renal tubular epithelial cells present in urine samples. Genome engineering of iPSCs is now routinely performed in the Core to introduce new variants and to convert disease-associated mutant alleles back to wildtype or use as controls. Skin biopsies (fibroblasts) or urine (renal tubular epithelia) will be procured from ATD patients or controls and the cells will be reprogrammed to produce iPSC lines. Genetically modified patient-derived iPSCs will be generated using genome editing techniques. In addition, the personnel in the Core provide assistance for investigators in performing genome engineering, particularly in the development of new techniques and reagents, and for the maintenance and differentiation of iPSC lines.

项目总结