 We're here at the nanotechnology conference here outside Tessaloniki at the beach party and hi, so who are you? So hello, my name is Gus Cusulas, spell KOU, SOU LAS. I'm an associate vice president for research and economic development for Louisiana State University and a professor of biology and biotechnology. I'm here to give presentations on my own research. That includes my work using herpes viruses for both vaccine purposes as well as therapeutics and vaccines for cancer, especially melanoma. So you give somebody herpes and then they have a solution against cancer? So currently the immunotherapy, which is really the prevalent therapeutic way of treating cancer There is a product in the market. It's marketed by Amgen Corporation. It's actually a herpes, a live herpes simplex virus type 1, the same virus that causes cold source in humans And this virus is injected into melanoma on the skin and it creates an anti-tumor immune response and alleviates that tumor. We have a similar product. We believe a much better product, a herpes virus, live attenuated. The same virus can be used for vaccine against herpes infections, both oral and genital, as well as ocular. But it can also be used to treat cancers, melanoma, breast cancer, prostate cancer, and ovarian cancer. So does that mean that the herpes is actually a good thing? Well, it's interesting. It's interesting because at least in experiments in mice, if the mice have been previously infected with herpes, then grafted melanoma tumors and then those melanoma tumors are injected with the virus, the therapeutic virus, you get a much better response because the pre-existing herpes infection makes the tumors more susceptible to killing by the incoming virus. So yes, the answer is more than 80% of all people are already positive for herpes simplex type 1. So the idea would be that those people would be even better treated if they had cancer with this particular product, which is also a herpes virus. So it's okay if you already have herpes or do you need to not have herpes and then get this solution? Both. If you do not, if you do have herpes, the prediction needs to work even better. But even if you don't, the virus is quite good in alleviating melanoma tumors, and we hope other tumors also. So herpes is not just a little thing on the lip. It's something deep in the body or? So herpes viruses, I tell my students that unlike true love, herpes is forever because it resides into neurons in a latent form and then when you stress it gets reactivated. We engineer the virus that cannot get into neurons. So if you really use this virus to do intramuscular vaccination, then you create a vaccine response that you can protect your body from incoming virus. If you're naive that these never saw the virus before, can also protect in a therapeutic way. So if you already had herpes virus and you get reactivations when you stress, the immune system is activated so you can control the virus from coming out from your neurons. So does this mean that the stuff you're doing with herpes is like an amazing solution kind of? Where is it like a door into the body to fix many different things? So viruses in general and herpes specifically really have evolved to take advantage of the body and infect different tissues. By using genetic engineering, we can engineer the viruses now to do good as opposed to really cause harm. So we can engineer them to become vaccines. We use them as vectors to be able to transfer other genes and antigens and create other vaccines. And in fact, I talked today in my presentation about using herpes virus, not only as a vaccine for herpes, but also a vaccine against malaria, which is a very important parasitic disease. We do that by cloning malaria antigens into the herpes virus. So when we immunize intramuscularly mice or guinea pigs, then they're protected not only against herpes, but also against malaria. This sounds like mind-blowingly awesome, is this at work? Is it just on rats only? How far is it from people? So right now, all this work is done preclinical, as we say. It's done in guinea pigs, in mice, in rats, and as well as in monkeys. The next phase is really human trials, phase one, phase two trials. We do have a company that I'm part owner that is actually about to submit studies for phase one, and phase one studies in humans is really toxicity studies, and then phase two are efficacy studies. We do believe because the product is already in the market for different purposes, and he has shown to be efficacious that there is a very, very likely that it will work in humans quite well. So how do you administer this medicine? I'm joking, but is it just by a case? Or no, I'm joking. How did they get it? So the medicine itself, the therapeutic, is done by injection intramuscularly. Now, if you talk about herpes infections, those are really transmitted by immediate contact through either saliva or genital contact and so on. So type one is a cold sort of virus, type two is a genital infection, and this is typically how it's transmitted. It's a very important disease, a social disease, because in the U.S. alone, there are over 300,000 of herpes simplex type two genital infections that creates a stigma, and it is forever, it can reactivate, cause pain, but beyond that it's more the social stigma that it carries that becomes very important, because it can break up couples and married couples and so on. There's no way to get rid of it, impossible. Well, you know, you could reduce the reactivation of the virus to very little. So basically, instead of having a virus in a reinfection and appearance, you know, once a month or once in six months, it could happen to you once or twice in your lifetime. So this is actually quite efficacious. To eliminate the virus, there's no current technology to actually eliminate that virus from the body at all. But how do you, how do you do the change from once a month to once or twice in your lifetime? It's because of the vaccine. So if your immune system is boosted, so it can actually create a much better control of the virus, then the virus remains latent, it doesn't come out. So the answer to this is to really boost your immune system. But with all the stuff you're talking about in the first seven minutes of this video. Oh, there's a dog. Okay. I hope he doesn't have a virus. This guy also. So, but in the first seven minutes of this video, you were talking about using herpes for good. Yes. So actually, instead of, you know, the advent of molecular biology and genetic engineering, we can engineer these viruses to become now vectors for good. So for therapeutics. In fact, that's what the product is in the market right now, because you could engineer the virus to become a vaccine for malaria, for tuberculosis, and for cancer. So this is the, the, not only herpes viruses, but in the US and around the world, a number of different viruses, including influenza, measles are now used that normally cause disease. Now they're reengineered to actually do good. You can really re-engineer viruses. Yes. So the virus is like molecules or something. So the virus, the herpes virus is a DNA virus, as we call it, double standard DNA, about 150,000 baspers. The entire genome, think of it as a chain of deoxyribulinic acid, can be actually cloned into a bacterium and replicated. And we use genetic engineering to modify that genome. And then recapture the virus. So in my own laboratory, we could create a brand new virus that has a gene deleted or a new gene inserted within a few weeks. So you take the DNA out of the virus, you hack it, you modify it, and you put it back. Yes. And it functions like a virus, but it goes and does something good. Other things, other things, exactly. Genetically engineered viruses. And this is like, people talk about this, so it's very rare. Are you the only ones who can figure it out? No, they're actually quite prevalent in the U.S. and a number of different viruses, not only herpes as I mentioned. A lot of other viruses are engineered to actually do good, to be able to use for gene therapy, lentiviruses, adenososciitis virus, using CRISPR-Cas9 to actually modify a chromosomal gene that's maybe mutated and cause disease. Other viruses are used as like herpes as for vaccine and other vectors. So how do you hack a genome? How do you go in there? It's not like there's only very little knowledge about this? No, actually, there is a tremendous advance in the states right now, using the CRISPR-Cas9 system. And that, in the conjunction with certain viruses like adenososciitis virus, a lot of people on research now are looking to repair bad genes. So viruses have evolved to become very efficient vectors, to transmit their genome into the cells and to even incorporate into the cellular chromosomes. So taking advantage of these properties, you can deliver a payload into cells as well as use them for repairing altered genome mutations that may cause harm. So there's DNA in the people, and there's DNA in the virus, and the virus goes and can do stuff in the body. Different viruses can do all different things, yes. So this is awesome, right? So who are you working with? Do you have students? Well, you know, my laboratory has approximately 20 people. A number of students are PhD students pursuing their doctoral philosophy. I do have postdoctoral fellows and research associates. We do have a number of core laboratories that do next-gen sequencing. So we can sequence the entire genome, the transcriptome, and we just did a lot in host-pathogen interactions. We just published late last year a review article on what we call first impressions, indicating from the moment that the virus touches the cell, the cell is very different, and we take advantage of these properties to really create better viruses that could do good, for instance, vaccine vectors and so on. So does this lead to personalized medicine, where you take the DNA of a person and also you figure out what's wrong with them, and then you target them specific medicine just for them based on their DNA? It's actually quite possible. For instance, a specific cancer can be sequenced, the mutations can be isolated, the genes that are affected can be isolated, and those genes can then be cloned into the virus, and then you can get a personalized vaccine, a vaccine that hopefully will work only for you because it specifically targets those bad genes, those bad proteins that have been changed through mutation. So it's a personalized virus just for you that fixes just you? This is mind-blowing if it works, and you're sure it works? Absolutely. I think it's already not only theoretically, but in practice, at least in preclinical studies, it's obvious, and this is really where personalized medicine is done. We actually find the exact condition, and the virus is only a vector system to be able to really help either create a vaccine response or transduce a gene and repair a specific gene. So think of a virus as a satellite of sorts. It's actually filled with cargo and can deliver it for different purposes. And you hear the nanotechnology conference here at the Saluniki. There's a little to do with nanotechnology. Is this all nanotechnology, what you're talking about? Exactly it is. So the viruses are really in micro-machines, but within the micro-machines, they have nanomachines that have specific mechanisms of attaching to cells, fusing with cellar membranes. So in essence, these really both micro and nano technologies that actually evolved over millions of years. In fact, if you listen to some of the lectures, one of the big basic principles in nanomedicine right now, nanotechnology, is mimicking nature. We call it mimetics or mimesis from the Greek word mimesis, where we look at the biological system and then try to create an artificial system, whether it would be nanoparticle, that would behave just like a virus. So all this can come to the market right very soon? How can we accelerate that because everybody wants this right? Well typically doing drugs in the U.S. takes anywhere from you know five to ten years to come in the market, even if it's accelerated, because obviously you have to go through phase one and phase two clinical trials and ultimately phase three trials that involves thousands of patients. So it's not a simple process. There are certain now efforts to try to shorten some of these steps, but still takes quite some time to develop a drug and put it in the market for wide use. Can you just do it over here in Europe like twice as fast and I'm joking? Yeah well you know actually my family, my sister-in-law is the CEO of the company Creative Pharma in Athens that do clinical trials. So yes you know clinical trials can happen in the U.S. and also in Greece. And this is what we all need to learn, that there's a lot of discoveries in the academic lab, but very hard to translate them into the marketplace and in the U.S. there are systems to do that more efficiently. Europe is kind of behind that, but I think they're hopefully they're catching up. And hopefully you have the solution? Absolutely, absolutely. I think we are very confident that next three to four years we're going to have a product in the market to alleviate herpes infections and additionally a herpes based product for at least for melanoma and hopefully for breast cancer.