2023 52 B3

CRISPR-Modulating Genes Involved in Insulin Sensitivity in Adipose Tissue to Treat Obesity-Induced Type 2 Diabetes

By: Breanna Paredes

Department: Biology

Faculty Advisors: Dr. Lily Chen, Dr. Nadav Ahituv (UCSF)

Obesity, a health concern based on excess white adipose tissue (WAT), decreases the quality of life in millions of people worldwide, and it is caused by poor lifestyle choices and genetics. Obesity is the primary cause of Type 2 diabetes mellitus (T2DM) because adipose tissue cannot adequately uptake blood glucose as an energy source due to insulin resistance. Since adipose tissue plays pivotal roles in energy storage, expenditure, and insulin regulation, manipulating adipose tissue for developing a T2DM therapy could be a potential approach for this disease. The Ahituv lab has successfully utilized CRISPR activation (CRISPRa) therapy that upregulates gene expression for therapeutic benefit, and it can be used to rescue various diseases. Here, we plan to use this approach to upregulate genes involved in insulin resistance in adipose tissue as a treatment for T2DM. We will design and optimize gRNA targeting these genes in human adipocytes and measure glucose uptake and insulin response in these cells. To examine the therapeutic potential of the therapy, we will inject CRISPRa-AAV (adeno-associated virus) into obesity-induced T2DM mouse models and then test for glucose tolerance and insulin sensitivity. In summary, this work will utilize CRISPRa in adipocytes to develop a novel therapeutic approach for T2DM.