 Genes are the entire basis of our existence. The tiniest change or mutation in our genes or DNA can lead to devastating consequences. One such consequence comes in the form of this disease called ADA deficiency. Now ADA or adenosine DMINase is essentially an enzyme which is crucial for our immune system. You see this enzyme, this ADA enzyme, it eliminates a molecule which is super toxic to the lymphocytes of our body. Now because of that, if there's not enough of this enzyme, this ADA enzyme, if there's not enough of it in our body, then what will happen? It will fail to get rid of that super toxic molecule and all the lymphocytes will start to die. And we cannot have that because our lymphocytes protect us from every possible foreign particle that you can think of like say viruses, bacteria, fungi, you name it and lymphocytes are protecting us from all of them. So do we have any solutions for this? Yes, yes we do. We do have some solutions for this condition. One of them is bone marrow transplantation. Now let's move this a little bit to the side so that you guys can see it. Now one of the options is called bone marrow transplantation. Now in this what happens is that you take stem cells from the bone marrow of a healthy person and then you inject it into the patient. Now stem cells are these cells which grow into a specific type of cell and the stem cells that we are collecting from the healthy person, these stem cells that we got from the healthy person, they will grow into new lymphocytes. So we are taking those stem cells and we're injecting it to the patient so that new lymphocytes can be formed in their body. Now if you don't want to go for bone marrow transplantation there's one more option. It's called enzyme replacement theory in which you inject the functional ADA enzyme directly into the patient. But neither of these, but the problem with these solutions what is I'll tell you is that neither of these solutions are, well they're not permanent. So the problem with now they say that like in some cases bone marrow transplantation has been somewhat permanent but there is no guarantee for it given that there's a huge list of side effects and sometimes you don't find the right donor who's going to donate that bone marrow for the transplantation. So because of a huge number of problems there's no guarantee that bone marrow transplantation is permanent and as for enzyme replacement therapy you have to regularly get that enzyme replaced technically. So you have to get that constantly done. So because of these non-permanent solutions this is where gene therapy kind of comes into the picture. Now what is gene therapy that's the first question that probably comes to your mind. Now gene therapy is this process or a procedure in which you replace the defective genes of something and you replace that with the functional gene. So you replace the defective genes with the functional ones. In this process what you are essentially going to do is that you will take the functional gene and you will deliver it to the patient and this new functional gene will compensate for that defective gene and end up producing that gene product which we desperately need. So that is the whole idea behind it. So you can kind of call it that it's a kind of a correction therapy where you are correcting that defective gene. So it's a form of correction therapy in one way but now the main question arises is probably that how are you going to do something like that. How are you going to pick out a gene and then insert it into that another person and then also make sure that that gene works perfectly in that person. So how exactly do you carry out something so complicated. Now ADA deficiency is one of the very first diseases where this gene therapy method was used for the first time. Now if you haven't already figured out by now but I'm mentioning it once again so that we are pretty clear about it. ADA deficiency this disease is caused due to a mutation like I said in the beginning like any tiny change can lead to huge devastating consequences. So ADA deficiency is also a result of a mutated gene and gene therapy seemed to be the perfect and this disease seemed to be the perfect place where gene therapy could be used for the first time and the approach that they used for ADA gene therapy is something called an ex vivo approach which literally is like if you translate this it's a Latin word actually and I looked it up it literally translates to out of the living. So what they essentially do or what they really do in this process in this ex vivo approach is that they take the cells extracted from the patient and then they modify them outside in a culture like in a plate or in a culture of some sort and they modify it and then they kind of injected back into the person so it's out of the living outside the living body that's why it's called the ex vivo approach. So here what they are going to do is that they will extract the lymphocytes from the bone marrow of the patient and they are going to then culture it separately in artificial conditions and allow these lymphocytes cells to multiply and grow and then what they are going to do is now they are going to add a functional copy of this ADA gene so you can see this green colored gene right over here let's change the color again so this this one this is the functional ADA gene the functional copy that we have and we are going to insert this functional gene into the cultured cells that we have the cultured lymphocytes with the help of a viral vector wait what now why you heard me viruses we use viruses as or viral vectors like as vehicles to transfer the gene but the question is are they safe is it safe to use a virus to transfer a gene well they can be whenever you use a virus as a vector of some sort you kind of get rid of all the harmful genes that can possibly cause some kind of complication in us that can possibly harm us so you get rid of all of those viral genes but the problem is that despite doing something like that in some cases these viral vectors have known to cause leukemia for some reason in in some cases in some patients so we couldn't have that if we wanted to use viruses as vectors we cannot have any kind of underlying complication that can arise from this virus or this viral vector so what scientists did they altered these viral vectors in such a way that they don't cause any form of cancer or leukemia or anything else for that matter so once they had altered these viral vectors so they kind of got rid of that extra problem that they kept facing once these viral vectors have inserted the functional ADA gene into the cultured lymphocytes we now take these now modified so these cells are now modified wait let's use a different color so we'll know so these cells right here they are now modified so we now take these modified lymphocytes cells and we inject them into the patient now what will happen when these lymphocytes are injected into the person is now that every single time a new cell is formed there will be this new functional gene copy that we had added earlier so every time the cell replicates or it grows or it multiplies then all of those cells will have this new functional copy and because of that the ADA enzyme will get perfectly produced something that the mutated gene could not do however no matter how cool this entire process seems and it seems pretty fancy and we're getting rid of the problem and stuff this entire thing was again not a permanent solution because think about it because these lymphocyte cells they are not immortal they're gonna die they're gonna perish at some point right and then what's gonna happen then these functional genes these functional ADA copies that we had added they would also die off with the right along with the cells so this person will need yet another jab of these modified lymphocytes that we had cultured in the lab these lymphocytes with the ADA gene with functional ADA gene and then he's gonna need another because those lymphocytes are gonna die and another and another so you get the idea right so it it's not a permanent thing again it's not then why exactly are scientists calling gene therapy so promising if it's not giving us any permanent solution then what's with all the hype right how why are we glorifying this entire process so much why does it hold so much of promise in the future that's because gene therapy has shown excellent results almost permanent results with stem cells now we already talked about stem cells earlier right so these cells can grow into a very specific type of cell so when scientists tried to do gene therapy with the stem cells that would eventually grow into lymphocytes something that we can find in the bone marrow like we had seen earlier that you find these stem cells that can grow into lymphocytes eventually and you can find them in the bone marrow so when scientists tried to do gene therapy with these stem cells then they saw that this ADA functional gene that they had inserted into those stem cells they expressed so well that the patient's immunity actually ended up improving so much more like there was apps there were absolutely no signs of any form of cancer or leukemia or anything else for that matter their immunity was really improved and the gene was getting expressed brilliantly the enzyme was getting produced just fine almost as good as normal so that is why we are calling gene therapy promising because when you are using gene therapy with stem cells they're giving us pretty amazing results for that matter almost close like as close to permanent as we can get so you see gene therapy is pretty darn amazing actually if you think about it I mean the medical field science has advanced so much all these years that we are trying to correct genes like genes not just the symptoms of a disease that's pretty huge if you ask me that's quite huge