期刊
ACS SYNTHETIC BIOLOGY
卷 10, 期 9, 页码 2231-2242出版社
AMER CHEMICAL SOC
DOI: 10.1021/acssynbio.1c00133
关键词
biomarkers; proteases; activity probes; nanosensors; synthetic biology; nanotechnology; cancer
资金
- National Cancer Institute [P30-CA14051]
- National Institute of Environmental Health Sciences, an Amar G. Bose Research Grant [P30-ES002109]
- Virginia and D.K. Ludwig Fund for Cancer Research
- Koch Institute's Marble Center for Cancer Nanomedicine
- NIH Molecular Biophysics Training Grant NIH/NIGMS [T32 GM008313]
- National Science Foundation Graduate Research Fellowship
The integration of nanotechnology and synthetic biology has led to the development of a gene circuit that can amplify biosensor responses to cancer states.
The integration of nanotechnology and synthetic biology could lay the framework for new classes of engineered biosensors that produce amplified readouts of disease states. As a proof-of-concept demonstration of this vision, here we present an engineered gene circuit that, in response to cancer-associated transcriptional deregulation, expresses heterologous enzyme biomarkers whose activity can be measured by nanoparticle sensors that generate amplified detection readouts. Specifically, we designed an AND-gate gene circuit that integrates the activity of two ovarian cancer-specific synthetic promoters to drive the expression of a heterologous protein output, secreted Tobacco Etch Virus (TEV) protease, exclusively from within tumor cells. Nanoparticle probes were engineered to carry a TEV-specific peptide substrate in order to measure the activity of the circuit-generated enzyme to yield amplified detection signals measurable in the urine or blood. We applied our integrated sense-and-respond system in a mouse model of disseminated ovarian cancer, where we demonstrated measurement of circuit-specific TEV protease activity both in vivo using exogenously administered nanoparticle sensors and ex vivo using quenched fluorescent probes. We envision that this work will lay the foundation for how synthetic biology and nanotechnology can be meaningfully integrated to achieve next-generation engineered biosensors.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据