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CRISPR-Based Gene Editing to Induce Thermogenic Adipose Tissue in Type 2 Diabetes

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Technical Report,15 Jul 2018,14 Jul 2019

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University of Massachusetts School Worcester United States

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This project seeks to use CRISPR-based deletion of specific target genes such as RIP140 in mouse and human adipocytes as a means to enhance browning and energy expenditure in these cells. Once this is achieved, the goal is to transplant such genetically modified, metabolically activated mouse or human adipocytes into normal or humanized mice, respectively, to enhance systemic glucose tolerance in diabetic animals. During this first year an exciting project achievement has been to develop and advance methods to optimize the efficiency of RIP140 gene deletion from about 50 percent which was the status at time of proposal to nearly 100 percent. This remarkably opportune advance positions us to progress toward our goals of alleviating diabetes in mice more rapidly than anticipated, and to quickly test the effects of deletions of other target genes that may also provide increased metabolism prior to transplant. We have thus exceeded our SOW goals for this first year by identifying RIP140 sgRNA that provides nearly 100 percent gene deletion in mouse adipocytes by CRISPR without the need for subcloning cells, and currently applying this advance to human adipocytes as proposed.

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  • Medicine and Medical Research

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