2019-047 – Engineering Stimulus-Responsive Effectors for Cell-Specific Control of Gene Expression

Background Currently, a significant research goal is to eliminate tumor cells while diminishing unwanted effects on non-tumor cells. Stimulus-responsive therapeutic systems (SRTS) capable of detecting cellular biomarkers are being developed to achieve this goal. After detection, the cells can be autonomously classified activating the payload, if tumor cells are detected. The payload can alter the genome of the cell or create an alternative output, resulting in an upregulation of tumor suppressors leading to induced apoptosis (cell death). Therefore, the enhancement of SRTS for specific biochemical environments is key in controlling drug delivery to tumor cells. CRISPR bacterial immune systems have been repurposed for genome editing in human cells as well as for therapies such as cancer treatment. CRISPR components can be engineered to both detect and activate gene expression in specific cells types. This could be used to deliver therapeutic payloads to cells with tumor-specific RNA biomarkers, reducing toxic effects on non-tumor cells. Thus, stimulus-responsive “smart drugs” utilizing the CRISPR-Cas9 system could specifically target tumor cells with therapeutic payloads to improve cancer therapy. Technology Description Researchers at the University of New Mexico have developed a stimulus-responsive therapeutic system (SRTS) based on CRISPR systems. A flexible and modular platform for diagnostic and therapeutic systems has been developed to autonomously decide whether to execute their programmed therapeutic function in response to local biochemical conditions. This dramatically reduces toxic effects on non-tumor cells, which is a major limitation to current clinical treatments. This technology will validate a new technological platform for engineering context-sensitive therapeutic systems, with a particular application in cancer therapy. This invention represents a new technology for stimulus-responsive CRISPR therapeutics that only activate in certain cell types. This will improve treatment options and outcomes for cancer patients, thereby reducing morbidity and mortality. Gregg Banninger GBanninger@innovations.unm.edu 505-272-7908

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