Tech Blog: Invention with Promising Future for Threat of Pandemics

Funded by NIH and the Packard Foundation, Michael Worobey, PhD, professor and department head of Ecology and Evolutionary Biology, and Tom Watts, senior research specialist and lab manager, set out to push the limits of genome sequencing. Their findings have the potential of enhancing our ability to fight pandemics.

For this month’s blog, we had the opportunity to sit down with Dr. Worobey and Watts. They took us through the idea that started it all, to where they are now and how their discovery could impact public health worldwide.

TLA: Thanks for chatting today. Could you tell us a little about the background of your invention?

Worobey: This came out of our work trying to recover HIV from very old samples where the genetic material of the virus is very degraded. We were working with samples that with conventional approaches for amplifying DNA and RNA, you would just get nothing, and so what we’ve developed is something that we call RNA jackhammering. We break the problem into tiny little pieces, which is an extremely sensitive way of piecing back together genomic information from degraded material.

Watts: One of the things that took us by surprise is that we were able to get full-length virus sequence from samples where there was no detectable RNA – it’s there but just in minuscule quantities.

Worobey: We’re applying this to samples that were going to be discarded by the NIH. NIH maintains a repository of a lot of the blood samples that were used to develop the first tests for HIV and we were contacted by them because they knew we were getting quite good a this. They basically told us they had great old samples that were important but there didn’t seem to be any HIV nucleic acids left in them and so we managed to get what we need out of all of those samples, which is pretty cool.

TLA: What problem does it solve?

Worobey: RNA jackhammering gives you a way to recover DNA and RNA of all sorts from samples that are either low concentration or damaged in some way. This is something we have developed with viruses in mind, but it will be of use for all sorts of different things including detecting low levels of mutations in cancer patients, allowing for earlier detection than other current methods. We have developed a foundational technique that should be useful across a wide range of problems. We’re interested in applying it to HIV cure research. The challenge with HIV is that we’ve had great success using antiretroviral drugs, but the problem is that the virus hides out at very low levels, even in successfully drug-treated patients, so if you take them off the drugs, it immediately rebounds back up to high levels. Our technique will help you tell if a patient still has those low levels of virally infected cells.

TLA: Who would be the top beneficiaries of a technology like this?

Worobey: This will have potential applications for viral diagnostics, HIV cure research to verify if someone is free from the virus, for oncology and early detection of cancer or relapse, and for resource-limited settings as well. This is a very inexpensive way of recovering genetic material and it’s something that can be applied in places where there is not a lot of money to throw at problems.

TLA: How will this invention change current standard practices?

Worobey: It has already changed the way we do recovery of genetic material from old samples. For many years our lab has led the way of in recovery of old HIV. We have clarified when, where, and how the virus originated by going back to really old samples and pulling genetic material out of them using these techniques. Shortly after we published our first paper describing the nuts and bolts of the method, we were in the midst of the Zika virus outbreak and so there were very high-profile papers that came out and took our technique and applied it to the problem of recovering sequence from Zika virus in more or less real time. As the epidemic unfolded, people were using our technique to generate genomic data that allowed us to understand what was happening. We expect that to be a standard tool in dealing with emerging infectious diseases.

TLA: What are you most excited about with this going forward?

Worobey: It’s an exciting time to work on viruses because there is still such an ongoing threat to public health worldwide. We’re really looking forward to shrinking the timeline from when you see the very first cases of something new and when you can generate data that will give you insights into how to stop it or control it. We’re most excited about using these tools so that in real time, you can catch things as they’re emerging and do something about them, rather than always reacting to a situation that’s unfolded beyond people’s ability to deal with it.

I liken it to a bucket brigade when a building is on fire in a village. Right now, we kind of react to emerging infectious diseases by forming bucket brigades. It’s great and everyone is pitching in and trying their best, but it’s really primitive. These techniques will help us move to something much more sophisticated that the threat demands. These pandemics—even a mild pandemic of a virus—can come with a trillion-dollar price tag. We’re building the tools that will help us prevent those. We’re also excited about using these techniques and other ones we’re developing in the lab to fight cancer. There are sort of Achilles heels in cancer cells that techniques like this can shine a spotlight on and so that’s another exciting area.

Learn more about Ultra-High Sensitivity Rt-Pcr for Viral Genome Sequencing, and connect with us for questions about this invention and licensing opportunities.