The World Health Organization reports that over 60 countries and territories suffer from continuing transmission of Zika, while the Centers for Disease Control (CDC) says that more than 40,000 people in the U.S. and its territories have been infected, including at least 4,750 pregnant women. With the growing danger of this infectious disease, and the impeding threat of neurological problems and brain damage it poses to developing babies, fast and accessible methods to screen for Zika and control its spread are urgently needed. One technology that promises to do so was the winner of the Nokia Sensing XCHALLENGE in 2013. Developed by Nanobiosym Inc., a Cambridge, MA firm, the Gene‐RADAR platform probes samples of bodily fluids placed on a “nanochip” and inserted into a portable device that rapidly reports the presence or absence of a pathogen. Following last week’s FDA Emergency Use Authorization of the Gene‐RADAR platform for Zika Testing, Medgadget had the chance to sit down with Nanobiosym’s founder and CEO, Dr. Anita Goel, a Harvard-MIT-trained physicist and physician.
Mohammad Saleh, Medgadget: Tell us about your Gene-Radar technology & Nanobiosym’s goals for healthcare.
Dr. Anita Goel, Nanobiosym: The bigger vision is to really bring the next generation of decentralized, personalized, and mobilized healthcare. Our Gene-Radar technology (which won the first X-prize in healthcare) is really the first model that moves in that direction. An example of this is our recent FDA Emergency Use Authorization for the first application of this platform for a more ‘real-time’ Zika test. It’s one step closer to the achievement of our bigger vision.
Medgadget: How does the Gene-Radar system work?
Goel: Our technology is essentially based on amplifying the detection of DNA or RNA. The underlying science comes from my own research pursuits to understand the physics of how nanomachines read and write DNA, that we have been working on at the Nanobiosym Research Institute. I have published some of the underlying science in journals like Nature Nanotechnology, Scientific American (India edition), and the Proceedings of the National Academy of Sciences. It represents a broader, 20-year research portfolio including multiple projects that I have served as PI on at Nanobiosym funded by DARPA, DOD, DOE, USAID, GCC, NSF, AFOSR, and NASA and CASIS. My training as a physicist and medical doctor from Harvard and MIT has enabled me to work at this nexus where physics, medicine, and nanotechnology converge. That’s really been the inspiration for some of the technological capabilities underlying Gene-Radar. In our commercial company, Nanobiosym Diagnostics, we’re trying to bring these technological capabilities to help address some of the biggest healthcare challenges on our planet right now, from a healthcare perspective.
Medgadget: How do you envision Gene-Radar enabling you to decentralize, personalize, and mobilize healthcare?
Goel: Well, the current paradigm of diagnosis is basically a centralized model of delivery. You go to your doctor’s office, they draw your blood or other body fluids, and they ship it to a centralized lab, for example on a FedEx truck. The centralized lab then performs gold-standard molecular testing using big machines that weigh several hundred pounds and can cost between a few hundred thousand dollars to a million dollars. They run your DNA/RNA molecular analysis (PCR, sequencing, etc), then the data comes back to your doctor’s office. Then you have to go back for a follow-up visit, and you get your prescription. This process, depending on where you are and what disease you’re being tested for, can take anywhere from days to months in the USA. There are 4 billion people on our planet today that don’t even have access to this centralized, highly bulky, diagnostics infrastructure available to us here.
Even here in the USA, we’re sort of on the verge of a multi-trillion dollar healthcare crisis. All the policies coming out of Washington DC might be nice, but they alone cannot solve these problems – we need transformative technologies, we need to upgrade our nation’s infrastructure and our global healthcare infrastructure. In the context of pandemics or epidemics like Ebola, Zika, influenza, you run into a situation where, even though we have some of the best centralized infrastructure, it starts to break down. In the case of the Zika crisis last summer in Florida, some places were doing up to 1,000 Zika tests per month! There was such a back-log of samples being sent to the centralized CDC lab that the wait time for a result could get as high as 5 weeks – imagine that for a pregnant woman waiting to find out if her baby is in danger.
Another example is a few years ago in the Ebola crisis, tax-payers in New York spent north of 20 million dollars for one Ebola case because our healthcare infrastructure was simply not equipped to handle these kinds of global health emergencies. FedEx trucks did not want to transport samples and the centralized labs did not want to touch it. So you’re left with a crisis where patients are entering a hospital and the hospital doesn’t know what to do because they don’t have the facility to test the patient on the spot but they need to quarantine them nonetheless. This, along with the public fear, creates quite a bit of chaos. In the case of a respiratory pathogen, you would really need a way to instantly test and quarantine infected patients. Having a rapid response technology, having a more mobilized, personalized, and decentralized testing capability for on-the-spot, real-time screening at an affordable cost is paramount to stopping the spread of a deadly pandemic.
Medgadget: Where do you envision this system being deployed, on the field in emergency outbreaks or at airports or labs?
Goel: Our vision is to eventually do both. The FDA Authorization we currently have is very limited to certain kinds of labs and only for Zika testing in the serum, as per FDA and CDC guidelines and protocols for how and when the test is appropriate. However, Gene-Radar as a platform could in the future accommodate other types of body fluids and we are currently considering doing the additional clinical trials for other clinical samples, such as urine or whole blood, to expand the applicability of the detection system.
Medgadget: You previously mentioned your vision for deploying Gene-Radar as a rapid-response diagnostic tool. Is the technology currently capable of detecting novel, yet-to-be sequenced pathogens?
Goel: The current generation of Gene-Radar looks for biomarkers that we already know the sequence for, so you would need to know the target before you go after it. However, our dreams for the future are bold. For now, the Gene-Radar 1.0 that we’ve rolled out does not involve any sequencing.
Medgadget: How does your Gene-Radar system differ from other diagnostic tools for Zika?
Goel: There are two flavors of tests for Zika. One looks at the antigen-antibody interaction – a serology test that looks for Zika-specific antibodies. These tests can have some non-specificity associated with natural antigen-antibody interactions, leading to potential false-positives. The other flavor of tests is nucleic acid based tests, looking for DNA/RNA sequences. Zika is an RNA virus, so we have sequence-specific recognition. In the case of Zika, serological testing can often show cross-reactivity with Zika-like viruses such as Dengue or Chikungunya and hence leads to high false-positive rates. The molecular tests look precisely at the RNA sequence and can distinguish between these diseases. We have done extensive studies with our Gene-RADAR Zika test and observed very clear profiles that minimize any cross-reactivity. This is based not only on our primer designs and how we do our amplification, but on our optimization of all aspects of the amplification process.
If you look at the competitive landscape for emergency use authorized PCR Zika tests, they tend to involve large, bulky, expensive platforms that can weigh a fifty pounds or higher. Our machine fits in your hands, is about the size of an iPad, and weighs 3.5 pounds. The FDA has not yet given us clearance to use it at the point-of-care. However, the footprint of our machine is like going from a big mainframe computer down to an iPad – it’s a step in the direction of our bigger vision to change the paradigm. We envision that our research into single-molecule diagnostics and nano-biophysics will enable smaller and smaller products.
The other distinction is that the other platforms can take several hours to produce results. We’re giving results back in about an hour, not including sample setup and preparation time, which is dependent on the operator.
Medgadget: What is the test’s limit of detection and false-negative rates? How does it fare for asymptomatic Zika-infected individuals?
Goel: The best way to compare those is to look at our Gene-Radar’s Zika Test Instructions for Use FDA document. The FDA supplied us with some reference samples and unknown standards for which we reported limits of detection. Because it’s a standard that can be used to compare across all available test platforms, you can see that we fare very well compared to other systems that use PCR-based detection. Zika is usually detectable in the serum for around two weeks, so this test system could still detect its presence in asymptomatic patients if they are tested in the correct window. If we expand the applicability of this system to other bodily fluids, we could theoretically expand this window of detection using our Gene-Radar technology.
Medgadget: Could you touch on the clinical trials performed before Gene-Radar was authorized by the FDA?
Goel: It involved the estimation and confirmation of limit of detection, reactivity and cross-reactivity testing, extensive in silico testing, and then a clinical trial that used real positive samples from infected patients, contrived samples where human serum samples are spiked with known concentrations of Zika virus, and negative human serum samples. They were all double-blinded and run in a head-to-head comparison with one of the traditional PCR-based assays.
Medgadget: How much does the Gene-Radar system cost?
Goel: We are still in the process of optimizing that. Our vision and dream is to make it affordable so that even the very poorest areas can have access to it. However, we still have to scale-up our production and we are working with an ecosystem of collaborators to figure that out. What we’re doing now is inviting people who want to partner with us on the roll-out and distribution of this to set the right pricing and generate an adequate supply.
Medgadget: What are some other next steps that will enable you to bring this technology to a wide user-base?
Goel: We’re very collaboration-based. We’re always working with potential customers, global health agencies, and hospitals. We’re working out exactly which new applications will be of greatest interest. Through our research incubator [Nanobiosym Research Institute], we have the ability to custom-build an app for those who might be interested. An example is to develop new personalized therapies for cancer through specific biomarker-based diagnostics. That’s on our R&D side. On the commercial side, we’re planning to focus on some of the most pressing infectious diseases and pandemics. We’re trying to get this tool ready, so that we could be helpful in the context of global and public health emergencies.
Medgadget: I’ve seen reports of interest in Gene-Radar from DARPA and NASA. Could you touch on those collaborations?
Goel: Our research institute has been funded multiple times by the US military, DARPA, the Department of Energy, the National Science Foundation, and NASA. Our most recent contract with NASA and CASIS aims to put some of our scientific research on the International Space Station (ISS). There are ideas on how we could, for example, one day put a Gene-Radar system on the ISS for analysis of astronaut health in real-time or, for example, use it to aid in the search for life on other planets. But that’s part of a bigger dream and vision. In the meantime, we’re hoping these collaborations can enable us to push the frontier of where physics, medicine, and nanotechnology converge.
Medgadget: Where do you see the nano-biotechnology field heading over the next few years?
Goel: Nanotechnology has been around for a long time, and it’s projected to become a 4.8 trillion dollar industry globally. But right now, it’s still for the most part sitting in universities and R&D labs. My vision for the Nanobiosym incubator was to help bring this new area of technology to the world so we can solve some of our biggest challenges in healthcare, energy, environment, clean water, food, etc. Our incubator focuses on bringing together a holistic approach using physics, medicine, nanotechnology, and information technology to create new science or technology, then incubate it all into different products and spin-off companies that can transform how we solve some of the world’s greatest challenges.
Here is Nanobiosym’s XPRIZE winning-video talking about the Gene-Radar technology:
Related press release: FDA Grants Nanobiosym Diagnostics Emergency Use Authorization for Gene-RADAR® Zika Virus Test…
Link: Nanobiosym homepage…