Multiplex 'Conditional' Mice for Rapid and Affordable Pre-clinical Testing

多重“条件”小鼠用于快速且经济实惠的临床前测试

• 批准号: 9195708
• 负责人: Branden S Moriarity
• 金额: $ 7.62万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-15 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9195708
• 关键词: Adult; Affect; Alleles; CRISPR/Cas technology; Cancer Model; Cells; Childhood; Clinic; Clustered Regularly Interspaced Short Palindromic Repeats; Complex; Control Animal; Cre-LoxP; Development; Disease; Enterobacteria phage P1 Cre recombinase; Evaluation; Gene Expression Profiling; Gene Targeting; Gene Transfer Techniques; Generations; Genes; Genetic Recombination; Guide RNA; Histologic; Individual; Injection of therapeutic agent; LoxP-flanked allele; Malignant neoplasm of pancreas; Methods; Modeling; Molecular Biology; Molecular Profiling; Mus; Mutation; Neoplasm Metastasis; Oncogenes; Patients; Phenotype; Plasmids; Pre-Clinical Model; Reaction; Research; Research Personnel; Resources; Ribonucleases; Safety; Site; Somatic Cell; System; Technology; Testing; Time; Tissues; Transgenes; Transgenic Mice; Transgenic Organisms; Tumor Suppressor Genes; Tumor-Derived; Western Blotting; aged; anticancer research; base; cancer therapy; cost; cost effective; drug testing; embryonic stem cell; homologous recombination; improved; mouse genome; mouse model; new technology; novel therapeutics; nuclease; osteosarcoma; plasmid DNA; pre-clinical; programs; promoter; public health relevance; repaired; research clinical testing; restriction enzyme; tumor; tumor progression; tumorigenesis; vector

 DESCRIPTION (provided by applicant): Mouse models of cancer have proven to be highly effective pre-clinical models for testing new cancer therapies for safety and efficacy. However, the generation of the most applicable mouse models of cancer is costly, time-consuming, and therefore not widely implemented. Generating new mouse models of cancer utilizing recently developed cutting-edge technologies will produce superior models in a more affordable and rapid fashion allowing new therapies to reach the clinic in a timely manner. To this end, we will optimize and implement a newly developed technology termed the CRISPR system. This system allows researchers to specifically delete or modify multiple portions of the mouse genome at one time in specific cells to induce tumor development. This model of cancer development as a pre- clinical testing platform is superior to current models as it is more rapid, cost effective, and easy to use. This will allow pre-clinical testing in accurate mouse models of cancer to be performed by many labs that do not have the resources to utilize the current mouse models, due to the aforementioned drawbacks. We propose to use the CRISPR system to generate new models of rapid onset osteosarcoma and pancreatic cancer, devastating diseases that affect pediatric and adult patients, respectively. All of the advantages of the CRISPR based models over traditional models will certainly attract many research labs to capitalize on the technologies potential in the field of cancer research and other diseases.



项目成果

Highly multiplexed genome engineering using CRISPR/Cas9 gRNA arrays.

• DOI: 10.1371/journal.pone.0198714
• 发表时间: 2018
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Kurata M;Wolf NK;Lahr WS;Weg MT;Kluesner MG;Lee S;Hui K;Shiraiwa M;Webber BR;Moriarity BS
• 通讯作者: Moriarity BS