NU 2021-259
INVENTORS
SHORT DESCRIPTION A customizable DNA based biosensor for detecting hypoxic environments
BACKGROUND Cell-based therapies have been successful in treating many malignancies, leading to substantial increases in patient survival. However, translating these successes to the treatment of solid tumors has been difficult for many reasons. Among these is the challenge of discovering distinct tumor antigens and developing biosensors against these targets. While this approach often leads to tumor specific therapeutics, the diversity of antigens across cancers results in only incremental progress with each new therapeutic. An alternative approach is to develop biosensors against characteristics of the tumor environment common across many malignancies. One such shared feature among tumors is the presence of a hypoxic microenvironment. Although some methods to restrict therapeutic delivery to hypoxic environments have been developed, such as fusing CARs to the oxygen dependent degradation domain of HIF-1a, these approaches suffer from a lack of sensitivity and can become active under non-hypoxic conditions due to leaky gene expression. A highly sensitive and tightly regulated hypoxia biosensor could enable tumor specific delivery of desired gene products by cell-based therapies.
ABSTRACT Northwestern inventors have developed a novel hypoxia biosensor that can rapidly detect hypoxic environments with unprecedented sensitivity. The technology is a DNA based system that consists of a hypoxia-sensing positive feedback loop coupled to expression of an output gene that becomes activated under hypoxic conditions. When this biosensor was integrated into both HEK cells and a mouse melanoma cell line, output gene expression was detected soon after the cells were placed in hypoxic conditions. This biosensor is highly customizable and can be tightly regulated by using an engineered transcription factor that is degraded in the presence of oxygen, decreasing the likelihood of leaky expression. Additionally, the modular nature of the biosensor enables signal amplification through strengthening the positive feedback loop, greatly increasing the sensitivity.
APPLICATIONS • Delivering gene products specifically to tumors via cell-based therapies • Monitoring tumor size in response to treatment via imaging
ADVANTAGES • Faster and more sensitive than current hypoxia biosensors • Less leaky expression under normal oxygen conditions
IP STATUS US application 18/993,319 filed.