It All Starts Here

Today we are continuing our discussion on gene therapy, with Dr Rajvinder Karda, hosted by Olivia. Raj is both a researcher and professor at the UCL Institute for Women's Health, with her role as an associate professor of Gene Therapy, as well as leading a team of research focussing on developing pre-clinical gene therapy and RNA editing treatments for childhood epilepsy, including Dravet Syndrome. Listen in to learn more about Raj's work in the field of gene therapy, as she explains more about how gene therapies are being researched and developed for pre-clinical trials, including in her lab where her team is working on the development of gene therapies for treating Dravet Syndrome.

Date of episode recording: 2025-01-22T00:00:00Z
Duration: 00:30:16
Language of episode: English
Presenter: Olivia Moir
Guests: Dr Rajvinder Karda
Producer: Olivia, UCL Institute for Women's Health, UCL Faculty of Population Health Sciences

What is It All Starts Here ?

This podcast provides the platform to bring awareness to various critical topics in the fields of reproductive science and women’s health – topics that are often not discussed enough. We will cover a range of topics and will focus on creating content that is understandable to individuals from all levels of education and backgrounds, with no science experience required.

00:00:02 Olivia

Hello everyone and welcome back to it all starts here, a podcast focusing on the communication and education of topics in reproductive science and Women's Health.

00:00:12 Olivia

I'm your host, Olivia Moir, and we are back here today to talk more about gene therapy. You might have already listened to our first episode on this, which featured Professor Simon Waddington, and he gave us a broad introduction to this field - and if you haven't, definitely go and check that out first.

00:00:31 Olivia

But today, we're going to be continuing that discussion with the wonderful Dr Rajvinder Karda. Dr Karda is both a researcher and professor here at the Institute for Women's Health. With her role as an associate professor of gene therapy, as well as leading a team of research focusing on developing preclinical gene therapy and RNA editing treatments for childhood epilepsy, including Dravet syndrome. Today's episode is going to dive more into her work on this and the applications of gene therapy in treating non-heritable genetic diseases.

And if you don't know what any of that means, don't worry, because we're going to dive into it today.

00:01:10 Olivia

So, it's such a pleasure to have you on this pod, Dr Karda.

00:01:13 Olivia

Genetics is truly such an interesting field and my favorite. And I can't wait to learn more about your work.

00:01:21 Olivia

So to start us off, please can you tell us a little bit more about where this all?

00:01:26 Raj

Of course, well, thank you first for that lovely introduction Olivia, and as you said, I'm Dr Rajvinder Karda. I'm an associate professor in Gene Therapy at the Institute Women's Health at UCL and to be honest, as a child I always loved science. I think I used to look forward to going to my science lessons in primary and secondary school and that kind of led me into doing a degree in biochemistry at King's College back in 2007.

00:01:48 Raj

And during that time, my passion for research really ignited. And so I continued my academic journey by doing a postgraduate degree in research at UCL as well, which was only at the Institute of Child Health at Great Ormond Street Hospital.

00:02:05 Raj

And this is really the first time I got involved into research, I was with patients, and I started to understand that some medicines like drug treatments are often inadequate and quite limited to some of the patients who have these very severe genetic disorders.

00:02:19 Raj

And so I started to get really intrigued and started research a bit more into gene therapy.

And so this led me to start in my PhD in Imperial College back in 2012 now, and my PhD really involved looking into using gene therapies at tool and looking for inflammation markers in a model for cerebral palsy and during my PhD, I was really interested in trying to develop gene therapy for a very specific neurological disorder.

00:02:48 Raj

And I came across Dravet syndrome from simply just researching and looking into different types of disorders there are out there. And back in 2015, there weren't many genetic therapies or people researching genetic therapies for Dravet syndrome, and because we knew there was a huge unmet need because in Dravet syndrome, current therapies were quite often inadequate and the disease is quite severe, with children with this disease.

00:03:14 Raj

So after a little trial error, I finally came up with some sort of genetic therapy for Dravet syndrome and in 2019 I applied for a grant application - It was successful and that kind of made me start, you know, developing pre-clinical gene therapies and RNA editing treatments for Dravet syndrome and since then, we've been able to use these kind of technologies and RNA editing technologies to develop treatments for other genetic epilepsies in children and other types of neurological diseases too.

00:03:43 Raj

So yeah, that's me in a nutshell essentially.

00:03:46 Olivia

So cool. I think it's. Yeah, I love how that started and it's sort of, It's so applicable I think, to so many people's lives where you kind of like see the more talked about diseases, you know when we're talking about careers in science or like careers in healthcare, you see the things that are often talked about, whether it's like in the media, or you've just heard about it one way or another, but then, these more kind of rare diseases that you know aren't just not talked about as much, or aren't researched as much and the importance of kind of looking into that. So that's really cool.

00:04:21 Olivia

So then sort of to back up a little bit for people that might not know as much about gene therapy, maybe we can get into that first and cover the basics. So further to that first episode that we did with Professor Waddington, let's talk about the different types of gene.

00:04:40 Olivia

So I guess there's viral and RNA editing and maybe you can touch on that a little bit.

00:04:46 Raj

So in order to explain gene therapy, we need to go back to kind of the central dogma of biology and what I mean by that is that you have a DNA which is essentially a genetic code, and that kind of forms RNA and then that forms your protein and everything's all fine and dandy. But if you've got a genetic mutation, so mutation in your DNA code, you have abnormal RNA and then you have abnormal protein in. This leads to genetic disease.

00:05:13 Raj

So essentially what gene therapy does, it comes along and it removes that faulty gene or replaces it with a correct sequence in an individual cells of that specific disorder.

00:05:23 Raj

And generally gene therapy does use harmless viruses to restore the function of that DNA.

00:05:31 Raj

And essentially what RNA editing does, if you go back to the central dogma biology, it interferes with the middle bit which is RNA and therefore interfering with protein. So, it's not directly impacting the DNA at all. So it's kind of fine tuning the therapy to only work on a small part of the RNA and therefore affect the protein production.

00:05:50 Raj

And in my team, we've developed this RNA editing treatment and essentially we also use it in harmless virus to essentially edit the RNA in individual cells and have a long lasting effect because if we use viruses, it’s a one off treatment and therefore in theory it should have a long lasting effect as opposed to if we were using a non viral therapy to do that.

00:06:11 Olivia

Right. Yeah. I mean it's all complex, but I think when you break it down, it's it becomes more clear. But then sort of like leading on from that of gene therapy. Why? I mean, you insinuated towards it, but, why is gene therapy important, like relative to other therapies that can be applied for different diseases? In something that's like related to your genes, let's say. What is the benefit of going directly to that source?

00:06:39 Raj

I mean, that's a very good question, I think the reason why gene therapies are really important is because a lot of these genetic diseasessome of them are rare, some of them not so much.

00:06:49 Raj

They have very limited or no treatment options and if you do have treatment options, they're often inadequate.

00:06:55 Raj

And a lot of these diseases cause very severe symptoms and sometimes people have life long disabilities and they do unfortunately die at a very young age.

00:07:03 Raj

And gene therapy offers a potential treatment to try and cure or actually reduce the symptoms that these patients have because there's literally nothing else out there and so.

00:07:13 Raj

It's another way of trying to treat these patients because unfortunately it's just it's really hard to.

00:07:17 Olivia

Yeah.

00:07:19 Olivia

Yeah, it's sort of like, would you say that it falls into the field of preventative medicine or not necessarily, because it's sort of like the, like, the diseased genes are already there.

00:07:32

Mm.

00:07:32 Olivia

So Gene, you know, therapy is going in to edit it.

00:07:36 Olivia

Is.

00:07:36 Olivia

It's almost preventative, I guess.

00:07:39 Raj

It can be, yeah, you.

00:07:40 Raj

You can edit the gene or you can kind of replace it with the correct sequence as well.

00:07:45 Raj

You.

00:07:45 Olivia

Right.

00:07:45 Raj

You could call call call it that.

00:07:47

OK.

00:07:48 Olivia

OK.

00:07:48 Olivia

Yeah.

00:07:49 Olivia

And then I guess in terms of like applications of gene therapy, so generally like you're looking at this specific 2 rare diseases. Where else could this be applied, for example?

00:08:00 Raj

I mean you can use it for non rare diseases.

00:08:04 Raj

Coming cancer is not is not rare.

00:08:06 Raj

Cancer is quite common, I think. I believe it's one in three or one in four people are likely to get cancer and there are gene therapies developed for this.

00:08:14 Raj

So it it can be applicable for not just rare diseases.

00:08:18 Raj

It really depends on where the need is, because a lot of these diseases.

00:08:20 Olivia

Right.

00:08:23 Raj

Have very limited treatments and that's a problem. You know, current drug therapies are not effective and therefore we need to use the technology that we have and really try to find a therapy that be quite effective. And I think the beauty about gene therapy is that.

00:08:35

Mm.

00:08:39 Raj

If you're using a viral gene therapy is A1 shot treatment because in theory if you give it once it should be there long lasting and you know we could touch upon the different examples later in this podcast. But that's essentially what gene therapy does.

00:08:43

Mm.

00:08:52 Raj

And so it it can.

00:08:54 Raj

It's tailored to that specific disease, which is key.

00:08:57 Raj

Because if you look at drug therapies, you get drug treatment.

00:09:00 Raj

And therapy drug therapy tends to suppress the symptoms or alleviate.

00:09:05 Raj

It doesn't actually go to the root cause of the disease, whereas gene therapy will go to the root cause of the disease and try to rectify that mutation and therefore in theory, that should be a long lasting effect than just getting a cocktail of drugs.

00:09:17 Olivia

Yeah.

00:09:18 Olivia

And would it be applicable to the individual? So like based on their genetic sequence or when you say gene therapy?

00:09:26 Olivia

It's more of like a broad treatment that targets your genes, but it's not specific to the individual.

00:09:33 Raj

Yeah, that's a good.

00:09:34 Raj

So it really depends on the patient population, so.

00:09:39 Raj

If a patient, if patients have all the same mutation, then we can use a very similar gene therapy applied to everyone.

00:09:46 Raj

But if you have a disease where patients all have very different mutations but do have a very similar outcome, similar symptoms outcome. In theory you could use the same gene therapy, right?

00:09:54

Mm.

00:09:58 Raj

But another scenario, if you have patients who have different mutations but have the different have the same disease.

00:10:05 Raj

Yeah, but have different symptoms. Then we got to tailor tailor the gene therapy for those individual patients and therefore it becomes a more of a, a different type of therapy.

00:10:14 Raj

Do and in in that kind of instance you probably would go to use gene editing for example, or even RNA editing to do that, because you have to make a more personalized medicine for that, right?

00:10:24 Raj

It really depends on the disease.

00:10:27 Raj

The patients with specific mutations and the types of symptoms they have and as gene therapists, we really look into the Natural History study of diseases to understand exactly how many patients have this mutation and how many patients present this type of.

00:10:42 Raj

Symptom and how that we can put that into our gene therapy and trying to find a treatment for it.

00:10:47 Olivia

That makes.

00:10:48 Olivia

So it's like tailoring the.

00:10:50 Olivia

Not just the actual therapy, but like the method of how that's going to be applied.

00:10:55 Olivia

Viral versus like RNA editing?

00:10:57 Raj

Yes.

00:10:57 Olivia

Based on the disease.

00:10:59 Raj

Exactly. Exactly because a lot of diseases have a spectrum.

00:11:02 Raj

And what I mean by spectrum is that they can have a different mutation or even have the same mutation represent a complete different symptom.

00:11:07 Olivia

Right.

00:11:10 Olivia

Right.

00:11:10 Raj

So it becomes difficult then, because you're like actually we can't use the same gene therapy for patient A with this disease.

00:11:17 Raj

With patient B, because they're presenting different symptoms and at that point you need to be like, right?

00:11:21 Raj

Need to.

00:11:22 Raj

We need to make this personalized.

00:11:24 Raj

We actually use a different technology to do that.

00:11:27 Olivia

Amazing. And then in terms of like broadly speaking the benefits of viral versus RNA editing, what would you say like if you were going to maybe give three key?

00:11:38 Olivia

Of each.

00:11:39 Olivia

1 You would use them for example.

00:11:41 Raj

So viral therapies are long lasting and you know the the most famous case of the viral therapies has been used is for spider muscular atrophy and spinal muscular atrophy is a very severe chartered neuromuscular disorder.

00:11:44 Olivia

OK.

00:11:52 Olivia

Right.

00:11:57 Raj

Where patients present very severe symptoms.

00:12:00 Raj

Such as unable to walk, unable to talk, they unable to feed or breathe on their own.

00:12:06 Raj

They do die, unfortunately, by the age of 18.

00:12:08 Raj

This is a very small lifespan. These patients have, and so a a a gene therapy using a virus was developed.

00:12:16 Raj

And this is simply by giving a single.

00:12:19 Raj

Administration to patients.

00:12:20 Raj

And after giving a single treatment, all these patients were able to walk, talk, eat by themselves and all live past 18.

00:12:28 Raj

And they're still doing follow on studies with these patients. And in fact this treatment was approved by the NHS in 2021.

00:12:35 Raj

This is readily available for children who were born with spinal muscular atrophy so.

00:12:39 Raj

A very good example of viral therapy was used for very severe neuromuscular disorder. Now only editing this two things you can do with that.

00:12:47 Raj

In my team we use RNA editing in a virus, so very similar to you would give one treatment or be long lasting.

00:12:53 Raj

But you can do these editing as non viral and so these will be repeated administrations.

00:12:59 Raj

They could be for they could also be for neurological diseases too.

00:13:03 Raj

It will.

00:13:03 Raj

You'd need to give it a few more times.

00:13:05 Raj

Won't just be a one off.

00:13:07 Raj

So those are the scenarios where you would use the different treatments depending on if you want it long lasting.

00:13:12 Olivia

Right.

00:13:12 Raj

Or if you wanted to repeat it to treat a disease over a period of time.

00:13:18 Olivia

OK. Umm.

00:13:19 Olivia

That makes sense. Thank.

00:13:21 Olivia

And then in terms of like the actual timing of applying these gene therapies, so in Java syndrome, this is already developed.

00:13:31 Olivia

It's like in early childhood. I guess the application would be of the gene therapy.

00:13:36 Raj

For giraffe syndrome, yeah, it it depends which giraffe.

00:13:36 Olivia

I.

00:13:39 Raj

The patients do present the disease around six months to a year of age and it really depends when they get diagnosed. So ideally you want to give the gene therapy as soon as possible.

00:13:49 Olivia

Right.

00:13:50 Raj

But they are, so they are.

00:13:52 Raj

There is a 2 clinical trials in fact for girvave syndr.

00:13:57 Raj

Um 1 is a non viral 1 is a viral therapy and this goes back to what we.

00:14:00 Olivia

OK.

00:14:02 Raj

So the viral therapy is using a a a harmless virus to deliver a sequence of DNA to rectify the genetic mutation in patients.

00:14:12 Raj

So they are delivering this gene therapy very early in development. So from the.

00:14:17 Raj

Of one to two eight years of age.

00:14:20 Raj

There's a multi center clinical.

00:14:22 Raj

So this is happening in the US, UK and Australia, whereas a non viral gene therapy has a larger age group.

00:14:25 Olivia

OK.

00:14:28 Raj

You're admitting the treatment to ages between 2 and 18 years of age.

00:14:33 Raj

But you're doing 3 treatments over a period of 6 to 9 months, and you're looking at the the.

00:14:36

OK.

00:14:38 Raj

Following the patients, seeing how it's working and the reason why that's happened is because.

00:14:40 Olivia

OK.

00:14:43 Raj

These types of non viral therapies have been used for Huntington's disease because those patients present it later in life and.

00:14:50 Raj

These number of therapies have worked in different types of diseases too, so the viral therapy has gone early in development because the spinal muscular clinical trial which I just discussed, they administer the the gene therapy very early in development. The first you know the youngest patient that rece.

00:15:10 Raj

Gene therapy, I believe.

00:15:12 Raj

Days of age I think the median age was 21 in the last clinical trial.

00:15:16 Raj

So what they've learnt is that the earlier you go with viral therapies, the better the.

00:15:21 Olivia

Right.

00:15:21 Raj

So that's why the age group for the viral therapies is smaller than for the non viral, which is 2 to 18 months of 18 years of age.

00:15:31 Raj

So you don't know, we're still looking at the outcome because it just started.

00:15:35 Raj

But we do know from the non viral therapy Drava syndrome, they've been able to reduce the seizures outcome in these patients.

00:15:42 Raj

That's a very good outcome for the Travis Indian community because it's working really well.

00:15:46

Yeah.

00:15:46 Raj

So you can see that there's different ages that they're administering it to and it's all about understanding how these mechanisms work.

00:15:53 Olivia

Definitely.

00:15:54 Olivia

And I guess like the other important factor that just came to mind as well is like in terms of the timing?

00:16:00 Olivia

So we said we're gonna talk a little bit more about it.

00:16:03 Olivia

We can do that now is.

00:16:06 Olivia

Diseases that are heritable versus non heritable.

00:16:09 Olivia

So Drove Syndrome is an example of non heritable, and so maybe like a background on what that means really, that's.

00:16:16 Raj

Absolutely.

00:16:17 Raj

So heritable diseases happen when there's a mutation in your germ cells, and germ cells are your reproductive.

00:16:23 Raj

So that means that this mutation will be permanent in Charles DNA and therefore will be passed on to the next generation.

00:16:31 Raj

Non heritable mutations happen in somatic cells and essentially these cells are non reproductive cells.

00:16:37 Raj

And these mutations happen by environmental factors or happen if there's some sort of issue with DNA replication that's occurred during development. But these mutations are not passed on to to the next generation.

00:16:49 Raj

That's the difference and with with Dravet syndrome, you know 90% of the patients have sporadic mutations that cause.

00:16:57 Raj

Their their disease itself.

00:16:58 Olivia

Yeah.

00:16:58 Raj

And that's what the difference is between the two.

00:17:00 Olivia

Yeah, that makes sense.

00:17:04 Olivia

You would see the disease presenting. I guess that's part of, you know, what leads to it presenting between 6 and 12 months of age.

00:17:11 Olivia

Said yeah.

00:17:12 Olivia

And then in terms of like, so two questions off that.

00:17:16 Olivia

So in terms of like.

00:17:18 Olivia

The gene therapy that you are administering to.

00:17:22 Olivia

A child, let's say.

00:17:24 Olivia

Is it different depending on if it's a somatic cell? So like if it's a non heritable disease versus a heritable disease, would the gene therapy be effective if it's heritable, like can you do that to reproductive cells for example?

00:17:40 Raj

So that's a good question, I think.

00:17:44 Raj

It's two questions you've asked there in terms of.

00:17:48 Raj

Talking about heritable diseases and using gene therapy and whether that affects the reproductive cells, right.

00:17:53 Olivia

Yeah, yeah.

00:17:53 Raj

It's two different.

00:17:54 Raj

So the first thing is the heritable gene.

00:17:58 Raj

Sorry, gene therapy, heritable diseases is the very good example of spinal muscular atrophy, right?

00:18:03 Raj

So as I mentioned.

00:18:05 Raj

And I think we talk about it quite a lot because it's such an amazing study that's happened and it's something that's unheard of with these children.

00:18:12 Raj

Is that spinal muscular atrophy is very severe that soon as a child is born, it will start to present the disease.

00:18:18 Olivia

Right.

00:18:18 Raj

And so.

00:18:20 Raj

They use a gene therapy for spinal muscularity, as I mentioned, which is a virus form, and gave a single administration to patients very early in development and they all were able to walk and talk on their own. And we live past 18 months, which is amazing because that.

00:18:35 Raj

Happened before.

00:18:37 Raj

So that's a good example where you can use gene therapy for heritable disease. Now using gene therapy to target reproductive cells is a very different subject, because that can be unethical because you can't really mess around with those.

00:18:48 Raj

Things and you know the studies that have ongoing where in pre clinical using animals to look into if you are trying to treat a disease are you targeting reproductive organs?

00:18:58 Raj

Because that's something we don't want to do, you know, and those things we do look into as researchers is we look into the reproductive organs and see are we?

00:19:00 Olivia

Yeah.

00:19:08 Raj

Are we infecting this with our gene?

00:19:10 Raj

Because actually we don't want to do that. What we want to do is actually treat the disease itself.

00:19:15 Raj

These are things that we do look into.

00:19:17 Raj

So yeah, so we don't use gene therapy to treat reproductive cells.

00:19:21 Olivia

Yeah.

00:19:21 Raj

What we do is treat the the disease that has happened because there is a.

00:19:27 Raj

I can't say the word.

00:19:28

Now.

00:19:30 Raj

It is.

00:19:31 Raj

It's a heritable mutation that's happened, and therefore it's caused this different type of severe disease and that's what we're trying.

00:19:37 Raj

Treat.

00:19:37 Olivia

Yeah, that makes so much.

00:19:39 Olivia

And then like in terms of, so targeting your therapy towards non reproductive cells, is there a way that you can do that?

00:19:49 Raj

Yes, I mean, I mean that's.

00:19:50 Raj

Of what we.

00:19:50 Raj

With all of all of the gene therapies.

00:19:54 Raj

So you know with, with spinal muscular, I keep going back to this is because it's a very good example to you.

00:20:00 Raj

It is mainly caused by motor neurons, so it's neuron cells that are.

00:20:05 Olivia

Yeah.

00:20:05 Raj

It just so happens that this mutation has been passed on from 2. Parents have a recessive gene for this particular.

00:20:13 Raj

SM1, gene, and therefore the babies born with spinal muscular atrophy.

00:20:17 Raj

And it's.

00:20:18 Raj

The most neurons that are affected by.

00:20:20 Raj

So those are not, they're not reproductive cells, they're actually neurons that are being targeted. And so therefore you are using gene therapy to fix a mutation that.

00:20:29 Raj

That is not in a reproductive cell, and in this case it's a motor neuron cell.

00:20:34 Olivia

Right. OK.

00:20:36 Olivia

Wow, I feel like I've learned so much.

00:20:38 Olivia

I guess, circling back to Dravet syndrome and your applications of gene therapy, we haven't necessarily established what currently is happening in the field of that and in your research work in particular, where are we at right now?

00:21:09 Raj

Currently there are many different groups around the world that are developed different types of gene therapies for Girvase syndrome.

00:21:16 Raj

And two of the pre clinical projects are happening in my team. So we've developed a a viral mediated gene therapies for both them are one is targeting a DNA one is targeting RNA and so at the moment we have.

00:21:24 Olivia

Yeah.

00:21:28 Olivia

OK.

00:21:30 Raj

Developing the treatment so that we can get all the experiments, all the right experiments done to make sure our both our treatments are effective before we take it on to a clinical trial.

00:21:39 Raj

So we're about four years away from getting to that point, but I'm hopeful that we can get this done because you know, there are many patients who are affected by this very severe disease.

00:21:49 Raj

Now, as I mentioned, there are two different types of therapies available in the clinical trial at the moment. So one of them is a non viral therapy.

00:21:56 Raj

That's the one that's been administered to patients between the age of 2 to 18 months, and they've shown some very good outcomes with it, able to reduce the very severe seizures that are happening in patients.

00:22:05 Raj

And they're just about to start their gene therapy clinical trial for Java syndrome, which is again is recruiting patients from the age of 1 to 8 years of age in the US, UK and Australia.

00:22:18 Raj

So like I said, this is a very exciting time for patients with Java syndrome and the driver syndrome community because.

00:22:24 Raj

You know, we know that.

00:22:25 Raj

It is a very severe childhood genetic disorder and we know that current therapies are.

00:22:30 Raj

Often inadequate, and you know they can.

00:22:34 Raj

Anesthesia medications can suppress the seizure frequency, but the seizures are still there.

00:22:40 Raj

You still have this.

00:22:42 Raj

Developmental delay and cognitive delay that does occur with these with this disease as well, so.

00:22:48 Raj

I'm very glad that there's different people working on.

00:22:50 Raj

I'm glad that we're working on it and we're trying to work towards trying to get these two patients as soon as possible.

00:22:54 Olivia

Yeah, definitely.

00:22:56 Olivia

And then I guess the other question that I would have like in this field of Drava syndrome, is there something that you find or even just gene therapy in general?

00:23:05 Olivia

There something that you find is a common misconception.

00:23:08 Olivia

Know whether it's with.

00:23:09 Olivia

Colleagues, or it's with, you know, your friends or family who maybe don't have a background. Like, do you find that there's anything that people will commonly just sort of assume? But you know, isn't true necessarily?

00:23:22 Raj

I I definitely it's a very good question because.

00:23:25 Raj

One of the things that they probably would be have misconceptions about is because when you talk about gene therapy, you discuss viruses as soon as you hear a virus because of the COVID pandemic, everyone's like, what is that?

00:23:38 Raj

It's almost a really bad thing.

00:23:39 Olivia

Yeah.

00:23:40 Raj

But if you don't know about gene therapy, you start to you. You would assume the worst of it because it's a virus.

00:23:46 Raj

But actually in fact, it's about educating everyone around you and educating the lay audience and also.

00:23:51 Raj

You know, a lot of parents who may not know about what gene therapy is and also just letting them know that it's it's it's quite safe because there's many different clinical trials going on for gene therapy at the moment and non viral gene therapy. You know both virus.

00:23:55 Olivia

Yeah.

00:24:04 Raj

Non viral. So there is a lot of data coming out showing that how safe it is and how it is.

00:24:10 Raj

Very effective in trying to treating very severe and.

00:24:12 Raj

You know all the way to treating cancer and different types of therapies too.

00:24:17 Raj

It's all about.

00:24:19 Raj

Feeding that information to the lay audience and letting them know that actually gene therapy is OK and it can be applied to many different disorders and help them in the long run.

00:24:24 Olivia

Yeah.

00:24:28 Olivia

Yeah. And I guess also like really kind of.

00:24:32 Olivia

Clarifying that point as well of like this is being applied to your somatic cells versus reproductive cells.

00:24:39 Olivia

And you know, I just, I feel like there's.

00:24:41 Olivia

Importance in like identifying and separating those two things.

00:24:45 Raj

Definitely.

00:24:47 Raj

And it's, yeah, it's about having these kind of.

00:24:49 Raj

We're really informed that to the wider audience because, you know, it's really important to do that as gene.

00:24:51 Olivia

Yeah.

00:24:56 Raj

We do get involved with a lot of patient groups because that helps us to feed an information to our research.

00:24:59

Yeah.

00:25:03 Olivia

Yeah.

00:25:03 Raj

Because we need to understand is OK.

00:25:06 Raj

How is this affecting the individual?

00:25:08 Raj

How is this affecting their?

00:25:09 Raj

Do we need to inform their parents too?

00:25:11 Raj

Going.

00:25:12 Raj

So it's it's a huge, it's a lot of people involved in into developing a gene therapy.

00:25:18 Raj

Not just what your research is is a bigger picture.

00:25:21 Olivia

Yeah.

00:25:21 Raj

We need to make sure this is everyone.

00:25:23 Raj

It works and everyone understands what's going on as well.

00:25:26 Olivia

Definitely. It's so important. And then also I.

00:25:31 Olivia

I have a question for you about, you know your specific field of study like like you said at the beginning.

00:25:36 Olivia

When you were kind of getting into this and you kind of, you saw the importance of looking into rare.

00:25:38

Mm.

00:25:44 Raj

Yeah, yeah.

00:25:45 Olivia

Diseases that maybe aren't as studied was that hard, like getting into a field that you know isn't as maybe funded or field that isn't as focused on or there isn't as many years of research, I mean.

00:25:59 Olivia

I'm sure that it presented unique.

00:26:02 Olivia

And do you have advice for anyone who you know, maybe is thinking about getting into that?

00:26:08 Olivia

Field or or just interested in you know.

00:26:13 Olivia

Maybe doing something that isn't done often?

00:26:16 Raj

Yeah. No, definitely.

00:26:18 Raj

I would encourage everyone to do it because you know at that time I was quite junior in trying to understanding what gene therapy.

00:26:24 Raj

I hadn't finished my PhD at that point and I didn't really know much about genetic epilepsies because my my my PhD had nothing to do with.

00:26:33 Olivia

Yeah.

00:26:33 Raj

And so really what I started to do was Googling.

00:26:37 Raj

I used Google quite a lot and Googled, you know, epilepsy experts at UCL.

00:26:42 Olivia

Yeah.

00:26:43 Raj

And I.

00:26:43 Raj

A lot of door knocking.

00:26:44 Raj

I went around, UCL said.

00:26:46 Raj

Hello I'm Raj.

00:26:47 Raj

Can you help me with this? And it was literally that.

00:26:50 Raj

Was me going around?

00:26:52 Raj

Just talking to people and people who.

00:26:53 Raj

Is this person that keeps coming around?

00:26:54

I keep.

00:26:56 Raj

But I was quite like determined that I wanted to learn.

00:26:59 Raj

I wanted to understand this and that didn't put me off in terms of there wasn't any research done, but I was like, well, if there isn't someones gotta do it, we've gotta figure it out. We have to figure.

00:27:00 Olivia

Stephen.

00:27:08 Raj

Out and it came to really establishing collaborations around everywhere because that's really key is like feed information to what I need to learn. And therefore I can understand how we're going to do this.

00:27:14

Mm.

00:27:20 Raj

And so that took many years to do that.

00:27:22 Raj

Really knocking on doors trying to get.

00:27:25 Raj

You know doctors who work with patients directly at great Arm St. Hospital to work with you.

00:27:28 Raj

That really fed into the whole research.

00:27:31 Raj

So it took a bit of time, but I will tell people to not give up.

00:27:33 Raj

Just literally requires.

00:27:35 Raj

There's a lot of going out there, networking, speaking to a lot of people, speaking to some experts in the field, getting as much information as you possibly can do to really formulate your ideas.

00:27:46 Raj

Honestly, it will be.

00:27:47 Raj

You know, I've I've done it. And many other people have done it too, but honestly requires patience and a lot of a lot of networking.

00:27:54 Olivia

So good to hear.

00:27:56 Olivia

OK. And then I guess to wrap things up.

00:27:58 Olivia

I mean in the field of Drava syndrome in particular, what are you hopeful?

00:28:04 Olivia

Like what are you hoping to see? You sort of mentioned like, you know, in the next 4 years, you're hoping to get it clinical?

00:28:11 Raj

Yeah.

00:28:11 Olivia

Your therapies, I guess that would be.

00:28:14 Olivia

What you're looking?

00:28:15 Olivia

But you know, even beyond that, what is the future of Java syndrome and epilepsy?

00:28:21 Olivia

Epilepsy and gene therapies look like for you.

00:28:24 Raj

Yeah. I mean, as I mentioned with Dravet syndrome, I'm I'm terribly excited about how the Phillips moving you know because.

00:28:32 Raj

There's two treatments available in clinical trial, you know for Travis injure and the nonviolent viral.

00:28:37 Raj

And we're developing some treatments too, and hopefully we should get that into into clinic in the next couple of years and as many teams across the world are working on different types of therapies for GAVI syndrome.

00:28:46 Raj

So it's a very.

00:28:47 Raj

It's an amazing time to work in gene therapy, but also you're seeing these really great outcomes from these clinical trials.

00:28:54 Raj

Really beneficial for the patient 'cause. That's the main thing is we're doing.

00:28:58 Raj

Benefit the patients with driver E syndrome because you know there's there's no other treatment that's working effectively.

00:29:04 Raj

Hmm. You know, current drug treatments aren't working really well.

00:29:09 Raj

In terms of the field, its work is moving in the right direction I believe, and I think as time moves on and as time.

00:29:17 Raj

Starts to develop.

00:29:20 Raj

We're starting to see that we can apply these gene therapies for many different.

00:29:23 Raj

So I think the field of gene therapy is going to move in, is going to vastly improve because so much is changing. As I mentioned, there's just, you know, your traditional gene therapy where you use viruses to replace a defective gene or using non viral therapy to.

00:29:37 Raj

Manipulate DNA. But you've also got, you know, new technology like gene editing or editing, where you can make much more precision medicine and try to treat different diseases.

00:29:47 Raj

So I think it's just gonna. It's gonna continue to grow and I and I honestly believe in my lifetime, at least I think you'll be able to buy gene therapy over the counter for something for sure. I think you will be able to.

00:30:00 Raj

I mean, we've already seen it with Covic.

00:30:02 Raj

Yeah, that was an M RNA therapy and also the AstraZeneca Advair. That was a gene therapy.

00:30:08 Raj

You know, I think people forget that some people in the population UK are very have received some form of gene therapy without realising they've.

00:30:15 Raj

It.

00:30:15 Raj

Yeah. So definitely, I think the field of gene therapy is going to vastly improve and change over the next couple of years.

00:30:22 Olivia

So cool. You heard it here first, guys.

00:30:25 Olivia

Thank you so much for coming.

00:30:26

You're welcome.

00:30:27 Olivia

It's been so great to learn from you.

00:30:28 Raj

You're welcome. Thank you for having me, it's been a really great chat.