The ease of genetically engineering mice has led to the development of disease model strains that precisely mimic human conditions. These strains provide the ideal testbed for evaluating novel therapeutic approaches based on genome editing. Our center provides a resource for researchers looking to take the first step into preclinical testing of novel therapeutic genome editing approaches in vivo. The GETC can help design and execute experiments with disease model strains that will allow a full evaluation of the efficacy and safety of innovative editing methods.
Mouse Strains
Baylor currently houses multiple disease model mouse strains amenable to gene editing-based therapy. Examples include the “wicked high cholesterol” of familial hypercholesterolemia, the Mdx model of Duchenne muscular dystrophy and the SOD1-G93A model of ALS. Visit Resources for a full list of models housed at the GETC.
Delivery Vectors
Our center has extensive experience with multiple vectors for the targeted delivery of genome editing reagents. We have successfully tested viral vectors, including multiple natural and engineered adeno-associated virus (AAV) serotypes, as well as adenovirus. We have also successfully tested lipid nanoparticles and amphiphilic peptides as delivery reagents for genome editing. Delivery routes include intravenous (both tail vein and retro-orbital), intraperitoneal, intranasal, and intratracheal, as well as oral gavage.
Testing Pipeline
Each experiment will be customized based on the disease model, editing mechanism, delivery system, and phenotypic readouts. Cohort sizes will be determined to ensure reproducibility. Unless the condition being studied is sex-linked, both sexes will be used. A typical experiment will begin with a health assessment prior to testing, body weight measurement, and a blood collection for plasma. Following this, experimental reagents will be administered, and the health of the treated animals monitored for the course of the experiment. After a sufficient amount of time has passed to allow maximum editing, a panel of organs will be assessed for both on-target and off-target editing. Histopathological analysis will also be performed on these tissues to observe any abnormalities, including immune cell infiltration. Phenotyping will be dependent on the model and strategy used but will generally include a molecular analysis to assess the restoration of gene function.
Proposing a Reporter Model Testing Experiment
To initiate preliminary discussions regarding a Disease Model Testing experiment, please fill out the form at the link below or email us directly at GETC-info@bcm.edu. Our personnel will contact you to set up a discussion to match your in vivo editing requirements with our resources and capabilities.
