Gene expression, the process that turns information encoded within the human genome into instructions for cellular and physiological function, is fundamental to all biology. Understanding gene expression is essential to the progress of medicine: the level of expression of specific genes gives clues as to whether an individual may be entering into the early stages of disease. Every day, scientists working in genomics understand the links between gene expression and human health more clearly.
Investigations into microRNA - a class of nucleic acids discovered only a little over a decade ago - have led to a new understanding of how an individual’s gene expression reflects his state of health. However, the powerful technologies used in other fields of genomics to quantify genetic material have proven cumbersome - arguably entirely unsuited - to measuring microRNA. This has hampered the field from making even more rapid progress. For example, it can take tens of hours and cost tens of thousands of dollars just to measure a single fingerprint of microRNA expression levels.
We propose to Genome Canada a partnership – in concert with the Prostate Cancer Foundation of Canada, the Ontario Research Foundation, the University of Toronto, and the Canadian Micro electronics Corporation - to build a platform technology ideally-suited to quantifying microRNA expression levels. In contrast with existing methods, the technology we propose to develop will cost under $10 per assay and will require 1 hour of operator time and an additional 1 hour of measurement time. Our technology will provide the sensitivity needed to work with samples already available in tissue banks. It will provide the dynamic range needed to quantify expression levels known to be relevant in genomics and clinical research based on microRNA.
Unlike existing platforms - which typically involve a number of enzymatic amplification steps, and often must measure light emitted from fluorescent probes - our chip will be purely electronic. The chip must simply measure the current that flows in a given microRNA-specific 'pixel' in response to the presence, or the absence, of that strand's complementary pair, the target of interest. The $5 camera chips in nearly ever cell phone sold today can sense as few as 5 electrons in each pixel; our circuits need far less sensitivity, requiring only 1000 electrons' worth of current flow per pixel to deliver research-relevant data. The project will strive for relevance to the Genome Canada platform community through quarterly calls with its Technology Development Advisory Board, made up of an internationally-acclaimed chemical biologist at Caltech; a Canada-based world leader in genomics and proteomics; and two industry experts with outstanding records of achievement in taking research innovations into clinical-research-relevant commercial production. We will engage in a close collaboration with the clinical research community, including one involving Dr. Fei-Fei Liu, a clinical oncologist based at Princess Margaret Hospital.
Project leader Kelley and her co-leader Sargent are intent on commercializing the technology. The prototype developed with the support of Genome Canada will provide a system that can be used to demonstrate the technology in order to raise Series A venture funding. Kelley has previously participated in fundraising for a successful clinical diagnostics company sold in 2006 for $232M.
Sargent recently attracted US$7.5M in venture capital to found an imaging company located in MaRS, a technology start-up incubator facility co-located with the University of Toronto and its affiliated teaching hospitals.
The social and economic benefits of the project reside in three categories:
(1) Economic growth.
(2) Improvement of health and quality of life
(3) Impact on public policy.
(1) Economic growth. The project led to the formation of spin-out company Xagenic. Xagenic, currently being incubated in the University of Toronto, has $1,000,000 of seed funding today, and employs five engineers and scientists. It is commercializing the inventions made with the Genome Canada support, in addition to several other agencies. Xagenic is addressing the multi-billion-dollar point-of-care molecular diagnostics market. It is seeking to attract Series A venture investment in order to build a ~ 20-person team, in a separate facility outside of UofT, to create a compelling prototype and successfully obtain FDA clearance and a CLIA waiver for its point-of-care infectious disease detection products. Ultimately, Xagenic seeks to grow into an operating company with a technology solution and price-point that positions it to build a multi hundred- million-dollar revenue stream from its base in Canada.
(2) Improvement of health and quality of life. The discoveries in the research project have led to two classes of findings relevant to the health of Canadians. Both relate to our proof of a convenient, cost-effective instrument and cartridge system that can detect the molecular signatures of disease. In relation to cancer, our system allows many nucleic acids biomarkers to be sensed in parallel, allowing a wide panel of gene expression to be followed accurately. This opens new avenues to screening patients early and cost effectively for the genetic fingerprints of cancers. In related work, we have proven that we can distinguish between different types of bacteria – thus showing in a model system that we can in principle tell the difference between antibiotic-resistance strains and less virulent ones. This addresses a crucial problem in Canadian hospitals – the rise of infectious diseases such as MRSA, VRE, and C. difficilie. Ultimately the inventions made through the project offer the capacity to improve both cancer care – through its early diagnosis – and the safety of our hospital system through effective screening of incoming patients at the point of admission for dangerous infections.
(3) Impact on public policy. The research results obtained herein have led to attention for research in devices for medical diagnostics devices in the Canadian and international media. Our findings, reported in Nature Nanotechnology in September 2009, led to significant attention. Media outlets included The Globe and Mail, The Financial Post, The Toronto Star, Nature, Nature Medicine; and Prof. Kelley was interviewed by Peter Mansbridge on the CBC’s Manbridge One on One.