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Week: 525.1 Guest: Luis da Costa- Research Fellow, Johns Hopkins Hospital Topic: The Gene Bomb- One Part Host: Steve Girard Producer: Ed Graham

NEMA: Surgery, when applicable, is the first line of treatment for cancers...take it out if possible...then there's radiation therapy, that kills large numbers of normal cells, and you have to know where the cancer is to irradiate it...then, chemotherapy, which also kills many innocent bystander cells, and causes a lot of side effects. Today, we talk with Luis da Costa, a research fellow at Johns Hopkins Hospital, about emerging cancer treatment technology...

da COSTA: Our intention here is to develop a system that will allow us to kill cancer cells specifically...without affecting normal cells. We've designed a system that we call a gene bomb that is basically made up of two genes. One of them acts as the explosive part of the bomb, and the other one acts as the control part, like a trigger or a detonator. And the trigger is designed in such a way that it can only be bound to proteins that would be present in tumor cells. So what happens is that there'll be a specific tumor cell protein that will bind the trigger, when it does so, it will set the bomb off. So, the cell will be killed..and the way we have it right now, neighboring cells will also be killed....there's a general problem we call gene delivery...so if you want to put genes into cells, its actually very hard...not all the tumor cells will take this up...but if we have a bomb that will kill not only that cell, but also the cells surrounding it, say if only five or ten percent of the cells in a tumor take that bomb, then we might be able to kill all the tumor.

NEMA: What's the mechanism that makes the bomb effective....

da COSTA: The explosive, let's say, is actually a gene that codes for a protein that comes from bacteria, so it won't be present in our cells. That enzyme converting a non-toxic chemical to a toxic chemical. So, what you do is That, after say, the cells have taken up the components of the gene bomb, you give the cells a chemical which is non-toxic, it won't do anything to them, unless they have the explosive part of the bomb activated. So, when the explosive part of the bomb is activated, the enzyme is activated, then it can convert this non-toxic chemical into something which is toxic.

NEMA: What do you see as the problems in implementing this therapy down the road.

da COSTA: The first problem is to maximize the specificity and efficiency of the bomb. As it is designed right now, there's still problems about how specific it could be...and whether the bomb could go off by itself. So, we have to work on that to make sure that's really fully safe. We also have to work on making sure that the levels of the proteins that are present in cancer cells are actually enough to set off the bomb.

NEMA: Unlike a drug, or radiation treatment, this therapy is more like surgery that's non- invasive.....is it aimed at a number of different cancers?

da COSTA: I like to think of this as a general model, so we just design one trigger that will bind the protein which is called p-53, which is a protein which is mutated in more than half of human tumors. But one of the beauties of the design is that you don't have to restrict yourself to this protein...you can redesign the trigger So, it could used in a wide range of cancers, with a wide range of protein abnormalities, let's say.

NEMA: Luis da Costa says he hopes that animal trials can begin using the technology within the next year...but it may be five or more years before any clinical human trials using the"Gene Bomb" are likely. I'm Steve Girard.

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Last modified: November 01, 2021