Using CRISPR to Diagnose Disease

I like to start with this image because it really highlights the unique diversity of various microorganisms but one thing that's in common for these microbes is that they all cause disease and actually over 200 years ago we didn't quite appreciate the connection between microbes and diseases in fact it was thought that epidemics were caused by a miasma or bad air and so people quite literally thought that you could get sick by inhaling the smell of rotting food now fast-forward to the mid-1800s when Louis Pasteur made they just got exciting discovery that bacteria could cause wine and milk to become sour and so he made us realize that if bacteria could actually make wine sick then perhaps they could also cause human disease today we have exciting technology that is capable of detecting and diagnosing diseases and in fact even cooler we've been able to harness bacteria themselves to develop diagnostic tools using a system called CRISPR so today I'm going to talk to you about two questions one I hope I can answer what is crisper and two how can we use CRISPR for diagnostics so we'll have to imagine ourselves in a tiny tiny test tube CRISPR is actually an ancient bacterial immune system that uses a cutting protein called Kass and a guide RNA molecule that is capable of finding a matching target sequence and bacteria typically use a system to defend against viral infections but we've been able to harness as tall as a powerful both Uniting and diagnostic tool because we're able to use the system to target specific sequences within a genome for some proteins the cutting doesn't stop there and so once it slices apart that initial target the protein keeps cutting and chops apart some of those reporter molecules that were shown in the video and we can design those reporter molecules to produce a color change when they're caught and so that forms the basis of using CRISPR as a diagnostic tool because you'll get a signal only when the target sequence is present so there are many flavors of CRISPR proteins and some of them are listed here so they're proteins called casts twelve casts thirteen and the most recently discovered cast 14 protein traditionally people have heard of the protein cast line that has been widely used for genome editing but these new variants of cast proteins are ones that contain this diagnostic capability that is able to give us a real-time readout when you have a target nucleic acid present in your reaction and so these systems all have their unique capabilities some of them like caste 12 and caste 14 are able to detect DNA and then there are others like house 13 which are capable of detecting RNA and so together these proteins make up our CRISPR diagnostics toolbox as we know it today but we continue discover new proteins that have unique features and advantages that we can leverage as novel diagnostic tools CRISPR itself is a really exciting and powerful tool because it has this guide RNA which is very easily programmable and this is one of the reasons why CRISPR has become so exciting in the field of both molecular biology all the way to medicine and so with youth with this system we simply design the guide RNA to target any DNA sequence and so you can imagine building a platform that that contains a CRISPR protein as well as let's say a library of guide RNAs that will target any sequence that you're interested in and so we can potentially go after a number of indications such as cancer screening detecting bacteria detecting viral infections and potentially even detecting antibiotic resistance we believe that CRISPR Diagnostics has the real potential to bridge the gap in molecular diagnostics and so traditionally we have kind of a large range of solutions that are out there we have rapid immunoassays that are typically very cheap and very fast at producing a result but they do suffer in their accuracy and then over at the other end of the spectrum we have molecular tests which are typically very expensive but also very high throughput and very accurate and so we believe that CRISPR Diagnostics fits right in the in the middle where we're able to leverage the advantages of rapid amino acids as well as the accuracy of a molecular test and so the key to making this a reality is being able to marry the the diagnostic capability of CRISPR along with a rapid and accessible format in order to address the key needs for Diagnostics so now I'm going to talk to you about three examples of where we believe CRISPR Diagnostics can make an impact and so the first example that I'll talk to you about today is human papillomavirus or HPV so HPV is actually one of the most common sexually transmitted infections and over 80 million Americans are infected by this virus and oftentimes getting infected by HIV HPV itself is not harmful but in certain cases there are specific HPV strains that can cause cervical cancer and so it becomes really important to be able to detect and distinguish these cancer-causing HPV strains and in fact we've already shown that CRISPR can detect and distinguish high risk versus low risk HPV strains and this is really important in order to stop progression of disease as well as reduce the risk of transmission another example is with staph infections so all of us are walking around with staph aureus on our skin and again normally this is completely harmless but in some cases the the staff artist can lead to serious infection that can lead to sepsis or even death and so in cases of staph infection it becomes really important to be able to distinguish methicillin-resistant sitive versus methicillin-resistant Staph also known as MRSA and so the gold standard today for detecting mrsa actually involves up to three days of culturing the bacteria to understand if it has this resistance and in the meantime patients are often prescribed broad-spectrum antibiotics and as you can imagine this can seriously exact exasperate the problem of antibiotic resistance and so we believe that if we had a CRISPR diagnostic we could be able to not only detect the presence of the staph infection but also indicate whether or not it has resistance that indicates that this is a versus strain and that allows for clinicians to make accurate and actionable clinical decisions within minutes instead of days and finally we can use CRISPR to also detect our own DNA so our genomes contain billions of letters that encode the blueprint of what makes us who we are and with the advancements of genomics we've learned that many diseases such as cancer have a genetic basis and oftentimes early detection of specific mutations can lead to better patient outcomes and better management of our own health and so one really well-characterized example of course is the bracken one and raqqa two mutations that are associated with breast cancer and so we believe that having the ability to detect these cancer mutations early and in a in a safe and you know actionable setting is key for allowing patients to take control of their own health and for for clinicians to help address these issues early on so at mammoth Biosciences we are really aiming to leverage the advantages of CRISPR to make people's lives better and in particular we believe that CRISPR diagnostics is very well primed to do that in fact Chris berry diagnostics may be the first CRISPR product that you'll see in the market because we're addressing a critical need that doesn't undergo the same types of ethical considerations as you might imagine with genome editing with CRISPR Diagnostics were able to leverage some key advantages of the system which allows you know diagnostic to be very fast affordable accurate and we're able to productize that in a way that can address key needs in a number of different areas beyond healthcare as well and so we envision a future in which CRISPR has the ability to provide actionable diagnostic information and in really empower individuals to take control of their own health and the health of their loved ones as well and with that thank you very much for your attention I'm happy to take any questions [Music] you [Music]

Channel: American Society for Microbiology

Views: 2,935

Rating: 4.951807 out of 5

Keywords: American Society for Microbiology, ASM, Microbiology, Science

Id: vhw7AeSc7vc

Length: 7min 47sec (467 seconds)

Published: Wed Jan 29 2020