1 00:00:00,000 --> 00:00:13,640 Thanks for joining us at the Canadian Breakpoint, a Canadian infectious diseases podcast by 2 00:00:13,640 --> 00:00:16,640 Canadian infectious diseases physicians. 3 00:00:16,640 --> 00:00:21,480 I'm Summer Stewart, back with Dr. Rupeena Purewal, pediatric infectious diseases physician 4 00:00:21,480 --> 00:00:23,280 in Saskatoon. 5 00:00:23,280 --> 00:00:29,240 Today we welcome Dr. Thomas Duchaine, founding director for the McGill Centre for RNA Sciences, 6 00:00:29,240 --> 00:00:30,240 to discuss mRNA. 7 00:00:30,240 --> 00:00:31,240 Dr. Purewal. 8 00:00:31,240 --> 00:00:37,400 Thank you everyone for joining us on another episode of our podcast, the Canadian Breakpoint. 9 00:00:37,400 --> 00:00:41,120 So today we have a very special guest with us and we're going to be talking about a 10 00:00:41,120 --> 00:00:45,360 lot about mRNA technologies, which we actually haven't done an episode on. 11 00:00:45,360 --> 00:00:49,880 So I am actually super excited to learn a lot from Dr. Duchesne. 12 00:00:49,880 --> 00:00:56,080 So Dr. Duchesne is a professor and chair of the Department of Biochemistry at McGill University. 13 00:00:56,080 --> 00:01:01,800 For more than 28 years, his research elucidated the genetic and molecular basis for the functions 14 00:01:01,800 --> 00:01:09,560 of mRNAs and non-coding RNAs in the control of gene expression across a diversity of physiological 15 00:01:09,560 --> 00:01:11,760 contexts and in cancer. 16 00:01:11,760 --> 00:01:19,480 A renowned expert on mRNA biochemistry and molecular genetics, his research program currently 17 00:01:19,480 --> 00:01:26,920 details how three prime untranslated regions of mRNAs and their interacting cofactors dictate 18 00:01:26,920 --> 00:01:31,120 mRNA translation, stability and decay. 19 00:01:31,120 --> 00:01:36,760 He mentored more than 40 trainees over the years, most of which later led careers as 20 00:01:36,760 --> 00:01:42,360 independent researchers or scientists in academia, as clinicians and in RNA related careers in 21 00:01:42,360 --> 00:01:43,360 industry. 22 00:01:43,360 --> 00:01:51,200 In most recent years, Dr. Duchesne led initiatives to translate deep expertise on RNA at McGill 23 00:01:51,200 --> 00:01:56,560 and in Quebec towards industry and clinical applications, among others by founding the 24 00:01:56,560 --> 00:02:01,080 McGill Center for RNA Sciences, which he currently directs. 25 00:02:01,080 --> 00:02:04,440 So thank you so much, Dr. Duchesne, for joining us today. 26 00:02:04,440 --> 00:02:05,440 We are super excited. 27 00:02:05,440 --> 00:02:07,640 We're going to talk a lot about mRNA. 28 00:02:07,640 --> 00:02:11,120 Yeah, I'm always ready for that. 29 00:02:11,120 --> 00:02:15,640 Of course. 30 00:02:15,640 --> 00:02:19,920 So just as a background, our listeners are healthcare professionals. 31 00:02:19,920 --> 00:02:22,940 We have nurses, physicians, trainees. 32 00:02:22,940 --> 00:02:28,560 So a lot of people, and I think just general audience that are interested in science and 33 00:02:28,560 --> 00:02:29,960 technology. 34 00:02:29,960 --> 00:02:36,100 So for background, can we maybe give our audience a bit of history on when mRNA was really introduced 35 00:02:36,100 --> 00:02:37,680 into medical therapeutics? 36 00:02:37,680 --> 00:02:38,880 Oh, yeah. 37 00:02:38,880 --> 00:02:41,240 I can give you a bit of a breakdown for this. 38 00:02:41,240 --> 00:02:46,960 For the common people and most of us out there, whether it's in the clinics or I know our 39 00:02:46,960 --> 00:02:52,960 daily lives all over the planet, RNA messenger RNA based therapeutics really became visible 40 00:02:52,960 --> 00:02:58,600 with the COVID-19 vaccines introduced, approved by the FDA in 2020. 41 00:02:58,600 --> 00:03:07,760 But for that form of prophylactic, like for many other therapies or treatments, you really 42 00:03:07,760 --> 00:03:11,680 have to look way back to really trace how this emerged. 43 00:03:11,680 --> 00:03:18,880 As a matter of fact, messenger RNA based therapeutics have been in the works for nearly 60 years. 44 00:03:18,880 --> 00:03:25,680 Since its very discovery in, I think it's 1961 actually, the messenger RNAs, people 45 00:03:25,680 --> 00:03:29,920 quickly realized the potential for their treatment, for the user's treatment. 46 00:03:29,920 --> 00:03:37,280 So really what we saw emerge in recent years is really the tip of the iceberg for about 47 00:03:37,280 --> 00:03:41,560 60 years of hard work by dedicated researchers. 48 00:03:41,560 --> 00:03:46,560 In Canada, just in Canada, for example, in our own backyard, there's the work, for example, 49 00:03:46,560 --> 00:03:48,400 Naomi Sunderberg and Jerry Peltier. 50 00:03:48,400 --> 00:03:55,840 McGill made us understand how messenger RNAs could be translated and used as tools. 51 00:03:55,840 --> 00:03:56,840 People like K.K. 52 00:03:56,840 --> 00:04:04,880 Ogilvie made the first chemically synthesized RNA, but also at UBC, for example, and this 53 00:04:04,880 --> 00:04:09,880 is a huge contribution directly applicable to the vaccines was the work of Peter Collis 54 00:04:09,880 --> 00:04:17,400 and his team at UBC on lipids, really, fatty acids that are so important to make those 55 00:04:17,400 --> 00:04:24,680 little bubbles of fatty acids that can bring RNA into cells. 56 00:04:24,680 --> 00:04:29,680 And when he presents his data, it's like 40 years of hard work where you had a hard time 57 00:04:29,680 --> 00:04:33,800 getting funded for that research, but that really is so important. 58 00:04:33,800 --> 00:04:38,960 But that was also in the US, as was celebrated with the novel in October, the work of Kathleen 59 00:04:38,960 --> 00:04:45,160 Carrico and Drew Wiseman, which really was a cornerstone of use of RNA as a vaccine. 60 00:04:45,160 --> 00:04:51,760 So Kathleen, actually, when she talks about in her novel lectures, she speaks of how hard 61 00:04:51,760 --> 00:04:57,000 it was to be funded on that research when nobody believed that RNA could be used as 62 00:04:57,000 --> 00:04:59,480 a vaccine. 63 00:04:59,480 --> 00:05:06,080 And Drew actually and Dr. Wiseman supporting her for believing in her vision for so long 64 00:05:06,080 --> 00:05:12,200 that led in 2005 really at the major breakthrough that allowed messenger RNAs from exogenous 65 00:05:12,200 --> 00:05:14,080 sources to be translated into cells. 66 00:05:14,080 --> 00:05:18,120 I'll talk a little bit more about this, but it's really a visionary contribution that 67 00:05:18,120 --> 00:05:21,720 allowed messenger RNAs to be used as vaccines. 68 00:05:21,720 --> 00:05:26,800 Beyond that, also, there's other major contributions that happened in most recent years. 69 00:05:26,800 --> 00:05:31,280 And in the background, people don't know about this, but there was Moderna working really 70 00:05:31,280 --> 00:05:35,320 hard on using RNA as a vaccine against cancer. 71 00:05:35,320 --> 00:05:37,000 Pre-COVID, this was going on. 72 00:05:37,000 --> 00:05:40,880 They were working on treatments of cancer based on messenger RNAs, vaccines against 73 00:05:40,880 --> 00:05:41,880 cancers, right? 74 00:05:41,880 --> 00:05:44,960 We would imagine for several years. 75 00:05:44,960 --> 00:05:51,200 And there are also other forms of RNA therapeutics that allowed this treatment that was going 76 00:05:51,200 --> 00:05:52,200 on. 77 00:05:52,200 --> 00:05:57,520 The RNA based therapy RNA LNP formulation was approved by FDA in 2018. 78 00:05:57,520 --> 00:05:59,240 It's another messenger RNA, but it is a RNA. 79 00:05:59,240 --> 00:06:03,880 And it was the work of the RNA Therapeutic Institute at UMass Medical School with a drug 80 00:06:03,880 --> 00:06:04,880 call on Trapel. 81 00:06:04,880 --> 00:06:10,640 And this really was, I would say, one of the cornerstones, stepping stones that the vaccine 82 00:06:10,640 --> 00:06:12,960 that we saw emerge. 83 00:06:12,960 --> 00:06:16,160 So for most of us, we say, hey, where did that come from? 84 00:06:16,160 --> 00:06:20,000 And how come it came to save so many people in the world? 85 00:06:20,000 --> 00:06:24,480 Did people just become a genius where they ignored this potential before? 86 00:06:24,480 --> 00:06:28,640 But it actually is the fruit of so much basic and discovery work. 87 00:06:28,640 --> 00:06:31,560 And people have really fought the hard fight for many years. 88 00:06:31,560 --> 00:06:36,040 I'm saying people, but it's also companies like Moderna and BioNTech that carried that 89 00:06:36,040 --> 00:06:38,160 ball for so many years in the shadow. 90 00:06:38,160 --> 00:06:41,160 But now we see it emerge. 91 00:06:41,160 --> 00:06:46,320 Being in the medical community during COVID, like you said, even myself coming up with 92 00:06:46,320 --> 00:06:51,360 mRNA vaccines, I think that was kind of our first exposure. 93 00:06:51,360 --> 00:06:59,600 And I mean, we learn about mRNA, of course, like in medicine, but never really translated 94 00:06:59,600 --> 00:07:05,600 how this could be kind of the future of some of the technologies that we, you know, mRNA 95 00:07:05,600 --> 00:07:06,680 based therapies. 96 00:07:06,680 --> 00:07:11,840 And so definitely, like myself, wasn't very familiar with it. 97 00:07:11,840 --> 00:07:17,280 So obviously, we've known about it for a long time, that these are the technologies. 98 00:07:17,280 --> 00:07:23,680 Is there any other reasons why we wouldn't have been able to bring about therapies or 99 00:07:23,680 --> 00:07:28,840 why are other companies, you know, like why was what was the difficulty with mRNA as opposed 100 00:07:28,840 --> 00:07:31,880 to kind of our other conventional therapies and models? 101 00:07:31,880 --> 00:07:37,440 Yeah, it's a very important question, because I think it's put the spotlight on how big 102 00:07:37,440 --> 00:07:41,320 of a contribution these folks I just mentioned and many others have made. 103 00:07:41,320 --> 00:07:46,200 I think it was on back burner for so long, because ARNI really, because of its chemical 104 00:07:46,200 --> 00:07:52,500 properties and how it interacts with cells, you know, there were a lot of barriers to 105 00:07:52,500 --> 00:07:55,360 overcome in order to use it as a drug. 106 00:07:55,360 --> 00:08:01,280 So there was so much time between the discovery of messenger ARNI and lipid nanoparticles 107 00:08:01,280 --> 00:08:06,900 and its ancestors, right, that used to be called liposomes and whatnot. 108 00:08:06,900 --> 00:08:12,840 There was so much delay that kind of fell on the back burner and some of these barriers 109 00:08:12,840 --> 00:08:15,920 really were overcome only in the recent years. 110 00:08:15,920 --> 00:08:20,480 So I'm talking, for example, about the chemical properties of ARNI. 111 00:08:20,480 --> 00:08:25,960 One of the key things is that I was different with DNA, it has a two prime hydroxyl group. 112 00:08:25,960 --> 00:08:30,440 So chemically, it's really something that is a handle and over it reacts really easily, 113 00:08:30,440 --> 00:08:33,080 it forms an intermediate that degrades the ARNI. 114 00:08:33,080 --> 00:08:36,760 So what my jargon essentially means that the ARNI is unstable. 115 00:08:36,760 --> 00:08:39,520 It's not meant to last forever, right? 116 00:08:39,520 --> 00:08:42,760 It's really a plan that you bring on the construction site. 117 00:08:42,760 --> 00:08:44,480 You're not supposed to keep it forever, right? 118 00:08:44,480 --> 00:08:48,960 It's something that's meant to be destroyed fast, right? 119 00:08:48,960 --> 00:08:50,480 Another issue is that it's polar. 120 00:08:50,480 --> 00:08:53,440 So you look at the chemical groups and that thing and there's no way it's going to enter 121 00:08:53,440 --> 00:08:55,000 the cell easily, right? 122 00:08:55,000 --> 00:08:56,920 So membranes are not polar. 123 00:08:56,920 --> 00:09:01,260 So ARNI really wasn't meant to be used as a drug at all. 124 00:09:01,260 --> 00:09:06,160 And usually when a cell recruit receives these signals from the environment, it's usually 125 00:09:06,160 --> 00:09:07,160 because you're in trouble. 126 00:09:07,160 --> 00:09:11,920 You either have broken cells or you have viruses around and you certainly don't want to have 127 00:09:11,920 --> 00:09:14,480 the virus ARNI getting into your cell. 128 00:09:14,480 --> 00:09:21,280 So there's a whole barrier also that the cell used to say, hey, this is not ours, right? 129 00:09:21,280 --> 00:09:22,720 And it's self versus non-self. 130 00:09:22,720 --> 00:09:26,800 So it's called innate immunity and there's several cascades, there are genetic programs 131 00:09:26,800 --> 00:09:30,940 that make sure that ARNI floating around doesn't get translated in your cells. 132 00:09:30,940 --> 00:09:36,280 So this is the discovery really that Keryco, Kathleen Keryco did in Wiseman. 133 00:09:36,280 --> 00:09:42,480 They figured out a way to change, use chemical modification on the ARNI to hide it from the 134 00:09:42,480 --> 00:09:43,480 innate immunity. 135 00:09:43,480 --> 00:09:45,740 So, and that's only 2005, right? 136 00:09:45,740 --> 00:09:47,880 That's a recent breakthrough. 137 00:09:47,880 --> 00:09:53,000 But the other challenge in distribution where we do overcome with the lipid nanoparticles, 138 00:09:53,000 --> 00:09:59,640 which is packaging these messenger ARNI's inside those lipid bubbles and making sure 139 00:09:59,640 --> 00:10:04,680 that it gets inside cells through routes that the cell use. 140 00:10:04,680 --> 00:10:13,480 You have many, many vesicles and lipoproteins that are uptaken naturally inside the cell 141 00:10:13,480 --> 00:10:18,320 and those LNPs use some of the machineries that those routes naturally use. 142 00:10:18,320 --> 00:10:23,560 So we started harnessing essentially those pathways to get stealth ARNI inside the cell, 143 00:10:23,560 --> 00:10:29,080 hide it from the immune system and this allowed the messenger ARNI to do its job inside the 144 00:10:29,080 --> 00:10:30,080 cell. 145 00:10:30,080 --> 00:10:33,520 So overcoming those barriers took a long time. 146 00:10:33,520 --> 00:10:38,520 And I think that that's why when these people were fighting the good fight, it kind of fell 147 00:10:38,520 --> 00:10:42,360 in the back burner in spite of the potential to a point where people like Keryco couldn't 148 00:10:42,360 --> 00:10:47,240 get funded and you really had the visionaries getting at it. 149 00:10:47,240 --> 00:10:51,760 So as to why we haven't heard about it until recently, I think it also was because the 150 00:10:51,760 --> 00:10:57,880 need to kind of just say that if you look at the so-called imbalance in death, it's 151 00:10:57,880 --> 00:11:00,680 about 20 million people that this vaccine saved. 152 00:11:00,680 --> 00:11:06,640 Not even mentioning getting back to work after the pandemic when we very understood the coronavirus 153 00:11:06,640 --> 00:11:09,160 and everybody was scared at home. 154 00:11:09,160 --> 00:11:13,600 This really came about quickly because there was a need. 155 00:11:13,600 --> 00:11:17,720 In a way, Rupina, I think about this and I think the most amazing thing about it is how 156 00:11:17,720 --> 00:11:24,760 fast and how well the humanity falls together and works together to overcome major challenges. 157 00:11:24,760 --> 00:11:29,920 They happen key points in humanity and we really can overcome major threats like this 158 00:11:29,920 --> 00:11:30,920 when we work together. 159 00:11:30,920 --> 00:11:35,120 And it's not only people, like I said, it's companies, it's university work, it's academia 160 00:11:35,120 --> 00:11:38,080 and industry and people and companies. 161 00:11:38,080 --> 00:11:42,360 It's just amazing how we can find solutions to huge demands like this. 162 00:11:42,360 --> 00:11:47,120 To me, it's another lesson of how people can collaborate to come up with solutions that 163 00:11:47,120 --> 00:11:48,840 impact the whole planet. 164 00:11:48,840 --> 00:11:51,920 And honestly, I mean, it's years and years of research, right? 165 00:11:51,920 --> 00:11:56,920 So it's not all of a sudden that these things come up like from what you're saying even 166 00:11:56,920 --> 00:11:59,360 now is that you have to work. 167 00:11:59,360 --> 00:12:02,680 If anybody's done research, they know that there's hurdles. 168 00:12:02,680 --> 00:12:10,600 There's a lot of ups and downs that you can have, but you really have to keep working 169 00:12:10,600 --> 00:12:18,240 at it because there is certain technologies and certain methods that over time you can 170 00:12:18,240 --> 00:12:20,500 excel at and fine tune. 171 00:12:20,500 --> 00:12:21,640 That's the key point. 172 00:12:21,640 --> 00:12:24,120 That's the key point, Rupina, and it's time, right? 173 00:12:24,120 --> 00:12:28,200 You need to keep your eyes on the long game and that's what research is about, biomedical 174 00:12:28,200 --> 00:12:30,600 research and discovery research. 175 00:12:30,600 --> 00:12:34,960 It takes a long time and it's not that and the application research. 176 00:12:34,960 --> 00:12:36,040 You need both, right? 177 00:12:36,040 --> 00:12:41,080 So otherwise you end up really quickly out of steam for innovation and not even mentioning 178 00:12:41,080 --> 00:12:45,040 the fact that you are outcompeted by other countries that do it properly. 179 00:12:45,040 --> 00:12:48,060 So what you're saying is exactly right. 180 00:12:48,060 --> 00:12:53,080 It's a matter of when you need things in the short term, you can mobilize, you can translate 181 00:12:53,080 --> 00:12:57,400 knowledge, but you need that depth of knowledge, quality of knowledge, and that comes with 182 00:12:57,400 --> 00:12:58,400 research. 183 00:12:58,400 --> 00:13:00,080 So you really should have both. 184 00:13:00,080 --> 00:13:01,080 Yeah. 185 00:13:01,080 --> 00:13:05,440 And so you mentioned some limitations, obviously, of the mRNA-based methods. 186 00:13:05,440 --> 00:13:15,040 Being unstable, you need money, funding to work it up and to also build these technologies. 187 00:13:15,040 --> 00:13:21,840 So what are some of the strengths that some of the mRNA-based methods provide compared 188 00:13:21,840 --> 00:13:26,080 to conventional methods that we use in other therapies? 189 00:13:26,080 --> 00:13:27,080 Yeah. 190 00:13:27,080 --> 00:13:32,080 So there are really two key points about RNA messenger RNA therapeutics that people should 191 00:13:32,080 --> 00:13:33,080 have in mind. 192 00:13:33,080 --> 00:13:38,320 And I think they reflect really, really well how they are disruptive and transformative 193 00:13:38,320 --> 00:13:43,800 for the whole drugs or therapeutics or prophylactic ecosystem. 194 00:13:43,800 --> 00:13:49,440 The most important point is that this is a new kind of drug, a new kind of treatment. 195 00:13:49,440 --> 00:13:51,080 It's an information drug. 196 00:13:51,080 --> 00:13:53,960 RNA in itself encodes things. 197 00:13:53,960 --> 00:13:56,000 It's information, right? 198 00:13:56,000 --> 00:14:00,840 So if you change the sequence of that RNA, you have a new drug. 199 00:14:00,840 --> 00:14:02,720 So chemically, it's the same thing. 200 00:14:02,720 --> 00:14:06,200 It's the same chemistry, the same RNA molecule. 201 00:14:06,200 --> 00:14:11,560 You're just changing that plan, what's written in their changes, and that changes in the 202 00:14:11,560 --> 00:14:14,000 case of a vaccine will have a new antigen. 203 00:14:14,000 --> 00:14:18,000 So you'll have a new target for a new virus, for example, just by shuffling the sequence 204 00:14:18,000 --> 00:14:21,600 to something that you want the immune system to target. 205 00:14:21,600 --> 00:14:26,960 But you can also encode other forms of messenger RNAs that have other purpose, so-called modalities, 206 00:14:26,960 --> 00:14:27,960 right? 207 00:14:27,960 --> 00:14:32,360 So you could, for example, program cells, the T cells, which is one of the modality 208 00:14:32,360 --> 00:14:33,920 called T cells. 209 00:14:33,920 --> 00:14:37,960 So you can essentially harness other forms of the immune system and direct it, let's 210 00:14:37,960 --> 00:14:40,000 say, to treat the heart disease. 211 00:14:40,000 --> 00:14:46,720 And we saw, for example, application like this last year in Nature, where they repurposed 212 00:14:46,720 --> 00:14:54,240 a lot of messenger RNA really close to the formulation that was used in the COVID vaccine. 213 00:14:54,240 --> 00:15:00,840 Messenger RNA and LNP was reformulated to program CAR-Ts, and they used it to treat 214 00:15:00,840 --> 00:15:07,160 overscarring issues in the heart disease and improve heart capacity after heart failure 215 00:15:07,160 --> 00:15:08,760 in the mouse system. 216 00:15:08,760 --> 00:15:14,460 So by changing the RNA sequence, not only do you have a new target for your immune system, 217 00:15:14,460 --> 00:15:17,280 you can even change a type of drug. 218 00:15:17,280 --> 00:15:21,600 It's extremely versatile, extremely powerful, because before when you develop a drug, you 219 00:15:21,600 --> 00:15:25,700 were limited to receptors and enzymes. 220 00:15:25,700 --> 00:15:28,620 And every time you develop a new small molecule, it took forever. 221 00:15:28,620 --> 00:15:31,160 You had to go through clinical trials and whatnot. 222 00:15:31,160 --> 00:15:33,880 So what I'm saying is that you have more targets also. 223 00:15:33,880 --> 00:15:39,440 You have far more therapeutic targets, not only for immunization, but also as potential 224 00:15:39,440 --> 00:15:40,440 drugs. 225 00:15:40,440 --> 00:15:48,480 And also, you fasten, you accelerate the process, because every time you have a successful vaccine 226 00:15:48,480 --> 00:15:54,080 or a successful RNA messenger RNA modality that works in the clinic, you de-risk the 227 00:15:54,080 --> 00:15:56,000 next innovation wave. 228 00:15:56,000 --> 00:16:02,640 So this ultimately, I think, is going to accelerate or at least change the game in clinical trials. 229 00:16:02,640 --> 00:16:07,640 I don't think it's going to happen right now, because these are new drugs and people are 230 00:16:07,640 --> 00:16:09,880 worried and they want to make sure they're safe. 231 00:16:09,880 --> 00:16:14,760 But I expect this to change the process of clinical trials, I think, in the mid-run. 232 00:16:14,760 --> 00:16:18,720 Of course, when you have new technologies, you want to play everything safe, make sure 233 00:16:18,720 --> 00:16:20,120 that people, it's acceptable. 234 00:16:20,120 --> 00:16:25,160 And you cannot make mistakes when you have this transformative kind of drugs. 235 00:16:25,160 --> 00:16:28,380 And I know companies like Modera, for example, are aware of this. 236 00:16:28,380 --> 00:16:30,840 And they're extremely careful in their clinical trials now. 237 00:16:30,840 --> 00:16:36,560 But I think at the mid to long run, we'll have to reinvent how those clinical trials 238 00:16:36,560 --> 00:16:41,200 are run financially and also in terms of also choice of disease. 239 00:16:41,200 --> 00:16:46,400 You have disease that are we call so-called orphan disease, because the courts are so 240 00:16:46,400 --> 00:16:47,400 here. 241 00:16:47,400 --> 00:16:52,520 There's so few people that have access to those clinical trials, because their clinical 242 00:16:52,520 --> 00:16:55,360 trial is expensive, but you also need large cohorts. 243 00:16:55,360 --> 00:17:02,320 And you can easily imagine how such a versatility and how easily you can repurpose them in the 244 00:17:02,320 --> 00:17:08,520 risk trials that you'll have cohorts and people that were equity seeking, just couldn't enter 245 00:17:08,520 --> 00:17:14,400 in clinical trials and just weren't the right subtype to favor the economics for the development 246 00:17:14,400 --> 00:17:17,400 of those drugs now having access to those therapies. 247 00:17:17,400 --> 00:17:19,600 So I give you three advantages. 248 00:17:19,600 --> 00:17:21,600 One of them is it's an information drug. 249 00:17:21,600 --> 00:17:23,160 You just change the sequence. 250 00:17:23,160 --> 00:17:25,400 You change the target, you change the modality. 251 00:17:25,400 --> 00:17:28,720 The repurposing that the risks, the clinical trials. 252 00:17:28,720 --> 00:17:34,220 And finally, I told you that some people or disease could not have access to the traditional 253 00:17:34,220 --> 00:17:40,720 form of clinical trials now, maybe gaining access to treatments that are based. 254 00:17:40,720 --> 00:17:41,720 Those are just three of them. 255 00:17:41,720 --> 00:17:45,840 But you can see how important this is going to be in the landscape for economics, for 256 00:17:45,840 --> 00:17:48,280 example, of pharmacistics and whatnot. 257 00:17:48,280 --> 00:17:49,880 This huge game changer. 258 00:17:49,880 --> 00:17:57,600 Yeah, very scalable, which is, I think, a huge advantage of an mRNA based method as 259 00:17:57,600 --> 00:18:05,520 opposed to, like you mentioned, having to change the entire framework of the therapeutic 260 00:18:05,520 --> 00:18:06,520 modality. 261 00:18:06,520 --> 00:18:07,520 Right. 262 00:18:07,520 --> 00:18:12,660 So instead of reinventing the wheel and going through the whole de-risking from A to Z, 263 00:18:12,660 --> 00:18:18,040 you build on previous success to de-risk the next step. 264 00:18:18,040 --> 00:18:22,000 Because it's what we call it drug repurposing, right? 265 00:18:22,000 --> 00:18:24,200 The greatest, I would say, level. 266 00:18:24,200 --> 00:18:29,360 And also as being in the medical community, first having scalability, that's really important 267 00:18:29,360 --> 00:18:34,120 because we're always looking for novel agents, especially as new diseases are coming up. 268 00:18:34,120 --> 00:18:36,440 Like you mentioned, there's rare diseases. 269 00:18:36,440 --> 00:18:42,200 And sometimes we're, because we have a lot of diagnostic testing, I think, that overall 270 00:18:42,200 --> 00:18:44,760 can find rare diseases now. 271 00:18:44,760 --> 00:18:48,800 But when we come to therapy, so even if you can diagnose them, if you don't have a therapy 272 00:18:48,800 --> 00:18:51,320 for them, it becomes challenging, right? 273 00:18:51,320 --> 00:18:52,320 When you're a clinician. 274 00:18:52,320 --> 00:18:53,320 That's right. 275 00:18:53,320 --> 00:18:56,960 And so it's all the concept of precision medicine, right? 276 00:18:56,960 --> 00:18:59,120 It was all the concept of precision medicine. 277 00:18:59,120 --> 00:19:03,920 You can stratify your disease, say, hey, you have this subtype of disease, this subtype 278 00:19:03,920 --> 00:19:06,680 of what do you do if you have nothing to treat it? 279 00:19:06,680 --> 00:19:07,680 Right. 280 00:19:07,680 --> 00:19:10,680 So you start a clinical trial for that rare subtypes, it's going to take forever. 281 00:19:10,680 --> 00:19:12,480 Nobody's going to get in a clinical trial. 282 00:19:12,480 --> 00:19:13,480 So it's pretty sad, right? 283 00:19:13,480 --> 00:19:17,080 So where you die, you have the wrong subtype, let's say cancer, the wrong subtype of cancer, 284 00:19:17,080 --> 00:19:19,240 and you're sorry out of luck. 285 00:19:19,240 --> 00:19:25,440 But with this now, you can have much smaller scale trials just because you can, on one 286 00:19:25,440 --> 00:19:31,040 hand, design a drug or vaccine against that type of cancer by just changing the sequence. 287 00:19:31,040 --> 00:19:36,800 And second, you have a lot of prior clinical trials to de-risk even smaller cohorts. 288 00:19:36,800 --> 00:19:38,520 And that's the key point, right? 289 00:19:38,520 --> 00:19:43,760 Because a lot of the fear and the scare comes from not knowing what the molecule is like 290 00:19:43,760 --> 00:19:45,600 and how we can utilize it. 291 00:19:45,600 --> 00:19:50,240 And so I think that's where if you have that information from other trials, that's the 292 00:19:50,240 --> 00:19:57,740 majority of what we do with research and as base or even when clinicians are using therapies, 293 00:19:57,740 --> 00:20:03,800 we look back at those research trials for assistance because we want to see how often 294 00:20:03,800 --> 00:20:05,800 did this therapy work, right? 295 00:20:05,800 --> 00:20:12,840 Because it's obviously, it's usually you're using it outside of the norm or not really 296 00:20:12,840 --> 00:20:18,040 off label per se, because it's probably, once Health Canada goes through the approvals, 297 00:20:18,040 --> 00:20:22,720 et cetera, then you have an indication for it, but you still have to resort back to clinical 298 00:20:22,720 --> 00:20:23,720 trials. 299 00:20:23,720 --> 00:20:26,420 So I think the research aspect is huge. 300 00:20:26,420 --> 00:20:31,200 The key thing though that you referred to, I think, affects also the general public, 301 00:20:31,200 --> 00:20:33,080 not only the clinicians. 302 00:20:33,080 --> 00:20:36,560 That's how fast this happens, right? 303 00:20:36,560 --> 00:20:39,940 How fast they emerge and we're just catching up to those new realities. 304 00:20:39,940 --> 00:20:44,200 So clinicians have science and they can refer to clinical trials, right? 305 00:20:44,200 --> 00:20:48,920 Even though it exploded in recent years, in 2020, I think there were a handful of those 306 00:20:48,920 --> 00:20:54,880 in the first year and now we're about 3,000 clinical trials that are MS and JARN based 307 00:20:54,880 --> 00:21:00,240 about, I think it's about 700 of them are against cancer. 308 00:21:00,240 --> 00:21:04,720 Cancer vaccine clinical trials, that's something that is completely new, you wouldn't think 309 00:21:04,720 --> 00:21:05,720 would be possible. 310 00:21:05,720 --> 00:21:11,600 Since 2020, now we have 700 clinical trials going on and I look at the data for these 311 00:21:11,600 --> 00:21:13,560 and they're very, very promising. 312 00:21:13,560 --> 00:21:20,480 Things like pancreatic cancer, for example, melanoma and sometimes that usually won't 313 00:21:20,480 --> 00:21:24,520 work now are actually within the range of those therapies. 314 00:21:24,520 --> 00:21:29,120 Concepts like new antigens are being used, for example, to make new types of vaccines 315 00:21:29,120 --> 00:21:30,680 against those diseases. 316 00:21:30,680 --> 00:21:35,800 It's currently exploding and both clinicians and I would say the general public have a 317 00:21:35,800 --> 00:21:41,240 hard time catching up and this will rightfully, I would say, raise some concerns or at least 318 00:21:41,240 --> 00:21:44,200 need to get access to the right information. 319 00:21:44,200 --> 00:21:48,400 I think, Rupina, that's why your podcast is so important because you're bridging that 320 00:21:48,400 --> 00:21:51,760 science with not only clinicians but general public. 321 00:21:51,760 --> 00:21:54,820 So thanks for doing what you do today. 322 00:21:54,820 --> 00:21:59,520 We still have a lot of catch-up, both clinicians, which would be called trial data, but also 323 00:21:59,520 --> 00:22:05,400 with the general public because when they're sitting at home and they're being told, now 324 00:22:05,400 --> 00:22:06,400 show your arm, right? 325 00:22:06,400 --> 00:22:11,320 And for the injection, you have something, you get injected in there, but now show me 326 00:22:11,320 --> 00:22:13,320 your children's arm. 327 00:22:13,320 --> 00:22:16,960 Show me your kid's arm so that we can inject those new technologies. 328 00:22:16,960 --> 00:22:21,920 We really do as scientists and caregivers and also I would say our policy makers have 329 00:22:21,920 --> 00:22:26,960 to listen, we have to hear, we have to listen from what's happening on the field and we 330 00:22:26,960 --> 00:22:29,560 have to understand those concerns so we can address them. 331 00:22:29,560 --> 00:22:34,440 We also need to educate ourselves to the science underneath and also the limitations of this 332 00:22:34,440 --> 00:22:38,000 science, not promising anything magical here. 333 00:22:38,000 --> 00:22:43,800 Anytime you put something foreign in an arm for injection, whether it's a vaccine or not, 334 00:22:43,800 --> 00:22:44,800 there are risks. 335 00:22:44,800 --> 00:22:45,800 There are risks. 336 00:22:45,800 --> 00:22:53,120 So, yeah, so the right question to ask is it perfectly safe? 337 00:22:53,120 --> 00:22:59,760 The right question to ask is, is it less risky than having a viral infection from a coronavirus 338 00:22:59,760 --> 00:23:02,600 that can kill? 339 00:23:02,600 --> 00:23:06,520 Another good question is, is it safer than what we currently have, for example, at the 340 00:23:06,520 --> 00:23:07,520 vaccines? 341 00:23:07,520 --> 00:23:10,280 The answer to those questions is by far yes, right? 342 00:23:10,280 --> 00:23:15,200 It was tested that the planet wide, you know, during the pandemic and these formulations 343 00:23:15,200 --> 00:23:20,560 of RNA and vaccines now we know are perfectly, not perfectly, but there's much safer than 344 00:23:20,560 --> 00:23:25,440 the prior modalities that we were using and far safer than being infected by this coronavirus, 345 00:23:25,440 --> 00:23:29,200 right, that the planet hadn't seen before. 346 00:23:29,200 --> 00:23:36,160 So I guess my point is about social acceptability, Rupina, not only for clinicians to use the 347 00:23:36,160 --> 00:23:41,160 full toolkit and understand and be able to answer questions to patients, but also in 348 00:23:41,160 --> 00:23:42,160 general, right? 349 00:23:42,160 --> 00:23:46,920 If you're not careful about this and you don't listen, you know, people will be worried and 350 00:23:46,920 --> 00:23:51,320 they will actually respond, right, by not accepting the treatment and you may have patients 351 00:23:51,320 --> 00:23:57,000 that end up suffering because they rejected that treatment or you'll get people on your 352 00:23:57,000 --> 00:24:01,800 parliament hill with trucks, with horns, because the policies, you know, weren't explained 353 00:24:01,800 --> 00:24:05,720 or the general public is not ready to accept something moving so fast. 354 00:24:05,720 --> 00:24:09,880 So it's a lot of words, but I think, you know, I'm touching upon the speed how these are 355 00:24:09,880 --> 00:24:14,000 implemented and I think there's an important challenge there following up on the strengths 356 00:24:14,000 --> 00:24:16,600 of these and potential of these therapies. 357 00:24:16,600 --> 00:24:19,560 Some of the weaknesses clearly have to do with social acceptability. 358 00:24:19,560 --> 00:24:24,840 Yeah, and I think we all face this, you know, whether it was from a professional or personal 359 00:24:24,840 --> 00:24:29,040 standpoint, you know, you always thought when the pandemic hit, I think it was everything, 360 00:24:29,040 --> 00:24:33,960 there was a lot of anxiety, there was a lot of, everything was very fast paced, right? 361 00:24:33,960 --> 00:24:39,840 So new disease, new learning environment, whether it was thinking about yourself getting 362 00:24:39,840 --> 00:24:45,840 the vaccine or giving it to others, like a lot of us clinicians became vaccine administrators 363 00:24:45,840 --> 00:24:49,760 at that time too, because that was just the, you know, and really weighing out the risks 364 00:24:49,760 --> 00:24:52,360 versus benefit, like you mentioned, right? 365 00:24:52,360 --> 00:24:54,600 And so that was the key point. 366 00:24:54,600 --> 00:24:55,600 Yeah. 367 00:24:55,600 --> 00:24:59,280 As a scientist, you're there, you go, you look at the papers and you read the papers 368 00:24:59,280 --> 00:25:02,320 and you say, oh, okay, that's what they know, that's what they're shooting in my arm. 369 00:25:02,320 --> 00:25:05,760 Oh, I see the chemistry here as a clinician say, okay, well, then, you know, they've had 370 00:25:05,760 --> 00:25:09,760 some prior trials, they can, you see on travels, you see, oh, this LNP is not really new. 371 00:25:09,760 --> 00:25:15,480 It's a messenger and so we have it, but the general public who doesn't have that science, 372 00:25:15,480 --> 00:25:16,480 right? 373 00:25:16,480 --> 00:25:21,520 They're blindfolded, they're blindsided and we're being asked to trust the government, 374 00:25:21,520 --> 00:25:22,520 right? 375 00:25:22,520 --> 00:25:26,280 In a really angst generating period with the pandemic. 376 00:25:26,280 --> 00:25:30,880 So yeah, you know, if you put yourself in their shoes, there's a lot of education to 377 00:25:30,880 --> 00:25:31,880 be had, right? 378 00:25:31,880 --> 00:25:32,880 With those technologies. 379 00:25:32,880 --> 00:25:37,440 I can tell you though, in my mind, there's absolutely no doubt that these technologies 380 00:25:37,440 --> 00:25:39,320 will just accelerate, right? 381 00:25:39,320 --> 00:25:45,720 They're talking about replacing the influenza vaccine that we get yearly, for example. 382 00:25:45,720 --> 00:25:46,720 This is going on. 383 00:25:46,720 --> 00:25:49,320 I mean, right now, you know, it's not very efficient. 384 00:25:49,320 --> 00:25:52,800 It's peptide based or I think it's, I don't know, virus based. 385 00:25:52,800 --> 00:25:54,840 So they're going to shift to Arnie. 386 00:25:54,840 --> 00:25:56,040 So it's just the start. 387 00:25:56,040 --> 00:26:01,160 So for the, you know, on one hand, we'll have messenger on the vaccines for things that 388 00:26:01,160 --> 00:26:03,280 we were exposed to before. 389 00:26:03,280 --> 00:26:08,000 But when there's a new pandemic, because there will be other pandemics upcoming, there's 390 00:26:08,000 --> 00:26:12,140 coronavirus and bats, you know, in Southeast Asia, there's going to be more that incubator 391 00:26:12,140 --> 00:26:16,360 and population is more mobile and we travel a lot. 392 00:26:16,360 --> 00:26:17,760 And we're more dense than ever. 393 00:26:17,760 --> 00:26:20,640 People are concentrated in cities more than ever. 394 00:26:20,640 --> 00:26:26,200 So and there's poverty and there's also, you know, all spectrum of, I would say, the cultural 395 00:26:26,200 --> 00:26:31,240 and practice that will affect distribution of those viruses. 396 00:26:31,240 --> 00:26:32,480 It's going to happen again. 397 00:26:32,480 --> 00:26:34,800 And guess to what they're going to turn next. 398 00:26:34,800 --> 00:26:39,200 They're not going to go backward with the technologies that, you know, were supplanted 399 00:26:39,200 --> 00:26:41,200 by the messenger Arnie vaccines. 400 00:26:41,200 --> 00:26:46,980 Rincon is going to turn to messenger Arnie's because it's faster, it's cheaper and it's 401 00:26:46,980 --> 00:26:51,680 versatile and you can reprogram and repurpose the modalities that were reliable before. 402 00:26:51,680 --> 00:26:56,480 So it's here to stay and it's going to replace and supplant many of the technologies. 403 00:26:56,480 --> 00:27:02,680 It's really, when you think about it, disruptive technology in the, you know, the meaningful 404 00:27:02,680 --> 00:27:07,520 sense of the word and the better we know about those as clinicians and scientists, the better 405 00:27:07,520 --> 00:27:13,520 we are to answer questions by mom, daughter, cousin, but also our patients as well. 406 00:27:13,520 --> 00:27:14,520 Right. 407 00:27:14,520 --> 00:27:18,140 And make them understand to the extent that we know, because we don't know everything 408 00:27:18,140 --> 00:27:19,640 about those still. 409 00:27:19,640 --> 00:27:20,640 Right. 410 00:27:20,640 --> 00:27:23,600 What are the risks and what are the advantages? 411 00:27:23,600 --> 00:27:24,600 And which is science. 412 00:27:24,600 --> 00:27:25,600 Right. 413 00:27:25,600 --> 00:27:26,600 So that is the evolution. 414 00:27:26,600 --> 00:27:27,600 Yep. 415 00:27:27,600 --> 00:27:31,200 And that is, and that's not only based on mRNA. 416 00:27:31,200 --> 00:27:32,240 That's anything. 417 00:27:32,240 --> 00:27:38,280 So we over time, and that's kind of why there's many steps of there's when you're doing a 418 00:27:38,280 --> 00:27:43,760 project, whether it's a small scale project or a large scale project, there's many milestones 419 00:27:43,760 --> 00:27:45,560 that you reach during the process. 420 00:27:45,560 --> 00:27:49,480 And then once it's out in the market, you also do a lot of post-market surveillance. 421 00:27:49,480 --> 00:27:54,920 And so I think that's kind of where the focus has been for my practice in my area with counseling 422 00:27:54,920 --> 00:27:59,560 is really, really letting people know that understanding that this is years and years 423 00:27:59,560 --> 00:28:02,400 of knowledge that's coming together. 424 00:28:02,400 --> 00:28:05,280 And not only that, we're still watching it. 425 00:28:05,280 --> 00:28:06,520 So there's an evolution. 426 00:28:06,520 --> 00:28:11,080 So I can guarantee that what I know today is what I'm going to know in 10 years, because 427 00:28:11,080 --> 00:28:13,440 that's not how science works. 428 00:28:13,440 --> 00:28:15,360 Science is always about knowledge and learning. 429 00:28:15,360 --> 00:28:16,360 Right. 430 00:28:16,360 --> 00:28:19,160 And so we're reflecting on this ongoing. 431 00:28:19,160 --> 00:28:24,360 And so what we know today about mRNA is probably much, much different than we knew about 40, 432 00:28:24,360 --> 00:28:25,440 50 years ago. 433 00:28:25,440 --> 00:28:27,360 So it's just fantastic. 434 00:28:27,360 --> 00:28:28,360 Absolutely. 435 00:28:28,360 --> 00:28:34,840 And there's a good system of checks and balance in science, but also in clinical applications 436 00:28:34,840 --> 00:28:36,720 and in therapy development. 437 00:28:36,720 --> 00:28:40,960 We really keep those with checks and balance. 438 00:28:40,960 --> 00:28:46,720 It's not to say it's a perfect system, but if there's flaws, they will be seen sooner 439 00:28:46,720 --> 00:28:48,160 than later. 440 00:28:48,160 --> 00:28:52,240 But this being said, I think that we need to keep an eye on those new technologies, 441 00:28:52,240 --> 00:28:58,080 that's for sure, and change whatever we need as soon as we capture any evidence of flaws. 442 00:28:58,080 --> 00:29:04,160 And I guess just to touch on that safety aspect, I always get questions around because this 443 00:29:04,160 --> 00:29:08,520 molecule is very unstable and we can change it in so many ways. 444 00:29:08,520 --> 00:29:15,720 Does it actually affect my own genetic makeup when I'm taking these vaccines or these treatments? 445 00:29:15,720 --> 00:29:18,360 And so what's your thoughts on that? 446 00:29:18,360 --> 00:29:21,320 Yeah, it's a question that I hear a lot. 447 00:29:21,320 --> 00:29:26,360 And I think it's very important for people to have a satisfying answer to that one. 448 00:29:26,360 --> 00:29:28,360 RNA is not like DNA. 449 00:29:28,360 --> 00:29:32,840 I know it's only one letter as an acronym, but fundamentally, chemically speaking and 450 00:29:32,840 --> 00:29:38,560 biologically, there's millions and millions, hundreds of millions of years of evolution 451 00:29:38,560 --> 00:29:44,040 made sure that RNA really had different purpose, a different biological purpose than DNA. 452 00:29:44,040 --> 00:29:49,360 DNA is something that you want to keep as a hard drive memory of who you are as a species 453 00:29:49,360 --> 00:29:51,960 and transmitted to next generation. 454 00:29:51,960 --> 00:29:57,360 Because RNA is really a blueprint, something transient and degradable. 455 00:29:57,360 --> 00:30:05,120 So RNA is, messenger RNAs anyway, are really meant to be read, used as a blueprint on site 456 00:30:05,120 --> 00:30:06,900 and then destroyed. 457 00:30:06,900 --> 00:30:11,560 It's actually on purpose that it's destroyable with that special chemistry. 458 00:30:11,560 --> 00:30:15,860 So when you inject a messenger RNA in the cell, it's not going to last very, very long. 459 00:30:15,860 --> 00:30:20,920 So keep in mind that there's about 400,000 messenger RNA in every single one of your 460 00:30:20,920 --> 00:30:22,360 cells right now. 461 00:30:22,360 --> 00:30:26,720 Every single one of your cells have 400,000 of messenger RNAs doing their job. 462 00:30:26,720 --> 00:30:29,000 They're not going back in your genome. 463 00:30:29,000 --> 00:30:33,720 They're actually read and destroyed and they're constantly produced from DNA. 464 00:30:33,720 --> 00:30:36,480 DNA's job is the memory. 465 00:30:36,480 --> 00:30:40,480 The messenger RNA's job is to be transient, read and destroyed. 466 00:30:40,480 --> 00:30:43,040 And it's very chemistry is make sure that it doesn't. 467 00:30:43,040 --> 00:30:48,240 There are really, really rare cases where RNA, and maybe that's part of the confusion, 468 00:30:48,240 --> 00:30:51,520 RNA can be reverse transcribed and inserted in genomes. 469 00:30:51,520 --> 00:30:55,960 And that's a job of rare viruses we call retroviruses. 470 00:30:55,960 --> 00:31:00,700 But that's because RNA can be also modified to play weird tricks. 471 00:31:00,700 --> 00:31:02,920 But that's not the messenger RNA's job. 472 00:31:02,920 --> 00:31:07,320 That's not what the chemistry and the biology of messenger RNAs do. 473 00:31:07,320 --> 00:31:11,560 And the ones that we use, the formulation or types of messenger RNAs that we use with 474 00:31:11,560 --> 00:31:17,000 its chemistry is really the product of about 60 years of intense study by millions of people 475 00:31:17,000 --> 00:31:18,000 worldwide. 476 00:31:18,000 --> 00:31:27,320 And there's groups working on the RNA in labs since the event, its discovery in 1961. 477 00:31:27,320 --> 00:31:28,880 So we know about messenger RNAs. 478 00:31:28,880 --> 00:31:31,120 They're not going back into your genome. 479 00:31:31,120 --> 00:31:34,800 It's really something that it doesn't do. 480 00:31:34,800 --> 00:31:36,920 And I think it's important for people to know that. 481 00:31:36,920 --> 00:31:41,520 And so we talked a little bit about the, obviously we're using mRNA based methods and prevention 482 00:31:41,520 --> 00:31:42,520 in vaccines. 483 00:31:42,520 --> 00:31:49,600 But you also mentioned that in treatment of diseases, for example, cancer would be a common 484 00:31:49,600 --> 00:31:50,640 theme. 485 00:31:50,640 --> 00:31:56,480 Are there specific diseases or like you mentioned for prevention, I think vaccines is kind of 486 00:31:56,480 --> 00:32:00,340 the key player there and influenza for the future. 487 00:32:00,340 --> 00:32:05,320 Are there other current modalities that are current therapies that are using mRNA based 488 00:32:05,320 --> 00:32:08,520 technologies that you'd like to mention to our audience today? 489 00:32:08,520 --> 00:32:09,520 Yeah. 490 00:32:09,520 --> 00:32:14,520 So I'm super excited about the cancer vaccines and what's cool about it, it's not only as 491 00:32:14,520 --> 00:32:17,680 prophylactic. 492 00:32:17,680 --> 00:32:22,320 We talk about vaccine as if they're prophylactic to prevent, but actually some of the clinical 493 00:32:22,320 --> 00:32:26,520 trials right now use cancer vaccines as a treatment. 494 00:32:26,520 --> 00:32:33,640 So there's one actually that was published in Nature in May, 2023, where, and that's 495 00:32:33,640 --> 00:32:37,960 actually really promising, there's a couple of others in parallel where what they did 496 00:32:37,960 --> 00:32:43,200 is they took the tumors, the patient's tumor, and they identified bits that are unique to 497 00:32:43,200 --> 00:32:45,220 the tumor and absent from the patient. 498 00:32:45,220 --> 00:32:46,680 So it's called neoantigens. 499 00:32:46,680 --> 00:32:51,200 So cancer shuffled the cards in a way that you can find bits of information there in 500 00:32:51,200 --> 00:32:56,480 the tumors that are not present in the rest of the patient. 501 00:32:56,480 --> 00:33:01,600 So you take this information and because RNA is so flexible and you can really generate 502 00:33:01,600 --> 00:33:08,400 a vaccine so fast, you generate a bank, a library of messenger nes that would immunize 503 00:33:08,400 --> 00:33:11,840 against those very same neoantigen. 504 00:33:11,840 --> 00:33:19,280 So you actually identify the Achilles heel of the tumor, you immunize while the patient 505 00:33:19,280 --> 00:33:24,640 is ongoing clinical trials, you immunize against its very own neoantigen and you can treat 506 00:33:24,640 --> 00:33:25,740 it this way. 507 00:33:25,740 --> 00:33:30,120 So it's not really the traditional prophylactic use of those, right? 508 00:33:30,120 --> 00:33:35,240 But eventually, what my understanding is eventually they will find some neoantigens that are common. 509 00:33:35,240 --> 00:33:41,360 That's in pancreatic cancer, you will find neoantigens that are multiple of those cancers 510 00:33:41,360 --> 00:33:44,800 and they may use it as a prophylactic as well. 511 00:33:44,800 --> 00:33:47,880 You were referring to other use of messenger netherpethics. 512 00:33:47,880 --> 00:33:55,280 There's for example, the self-programmable form of cells that we call CAR T. So they're 513 00:33:55,280 --> 00:33:58,280 essentially, yeah, you probably heard about this. 514 00:33:58,280 --> 00:34:03,520 They're cell-based messenger netherpethics and the idea there is to program the immune 515 00:34:03,520 --> 00:34:06,720 system to redirect it to serve different purposes. 516 00:34:06,720 --> 00:34:10,100 There's huge potential for messenger netherpethics there as well. 517 00:34:10,100 --> 00:34:15,920 It's another so-called modality and it can go and treat things like heart disease, for 518 00:34:15,920 --> 00:34:18,040 example, just to name one of them. 519 00:34:18,040 --> 00:34:23,440 So the different modalities are based on messenger netherpethics are quite diverse and there's 520 00:34:23,440 --> 00:34:27,400 also flavors of messenger netherpethics that are in development, things like self-implifying 521 00:34:27,400 --> 00:34:28,400 messenger RNAs. 522 00:34:28,400 --> 00:34:33,560 So you add a bit of information, the RNA so that it stays longer, you amplify the messenger 523 00:34:33,560 --> 00:34:40,760 RNAs or circular RNAs that are messenger RNA linear, you have a 5' and 3' and it's part 524 00:34:40,760 --> 00:34:45,600 of its behavior but you can also make it a circle and the RNA lasts longer this way. 525 00:34:45,600 --> 00:34:48,800 There are many, many uses for the different forms of RNAs. 526 00:34:48,800 --> 00:34:54,120 They're apparent to messenger RNAs but there are different modalities I would say that 527 00:34:54,120 --> 00:35:00,440 are emerging that can modify the pharmacokinetics and pharmacodynamics but also the types of 528 00:35:00,440 --> 00:35:03,360 targets that you can challenge with those therapeutics. 529 00:35:03,360 --> 00:35:08,600 All of this is different level of development but I think the first essay, the self-amplifying 530 00:35:08,600 --> 00:35:11,760 RNA was just approved by FDA a few weeks ago as a matter of fact. 531 00:35:11,760 --> 00:35:17,240 So all these are different stages of development but they will emerge in therapeutics soon. 532 00:35:17,240 --> 00:35:18,240 Okay. 533 00:35:18,240 --> 00:35:23,160 So the vast majority of indications definitely when we're looking at kind of what we're targeting 534 00:35:23,160 --> 00:35:26,840 and also what these modalities will be eventually be used for. 535 00:35:26,840 --> 00:35:28,640 So a lot of ongoing research. 536 00:35:28,640 --> 00:35:29,640 Yeah. 537 00:35:29,640 --> 00:35:30,640 That's awesome. 538 00:35:30,640 --> 00:35:31,640 Yeah. 539 00:35:31,640 --> 00:35:32,640 Well, there's a lot of other modalities also. 540 00:35:32,640 --> 00:35:33,960 There's the SI RNA base. 541 00:35:33,960 --> 00:35:37,520 They're not messenger RNAs but they're RNA base like CRISPR for example where you engineer 542 00:35:37,520 --> 00:35:43,360 the genome and can change your cells forever but there's also lots of cool research done 543 00:35:43,360 --> 00:35:47,840 in chemical biology, new modifications of RNA, adding bits of sequence to the RNA so 544 00:35:47,840 --> 00:35:50,800 that we decide where and when the RNA is expressed. 545 00:35:50,800 --> 00:35:53,200 You know, I work on true prune untranslated regions. 546 00:35:53,200 --> 00:35:56,840 Those bits of information decide where the messenger RNA works really. 547 00:35:56,840 --> 00:36:01,840 And there's a lot of cool stuff done on lipid nanoparticles and other nanoparticles. 548 00:36:01,840 --> 00:36:08,120 Again, the delivery of the RNA is a huge challenge and you know, not only from microkinetics, 549 00:36:08,120 --> 00:36:13,360 from microdynamics to which tissues it goes, how long it distributes, you can even change, 550 00:36:13,360 --> 00:36:16,560 tweak the response of the immune system by changing the lipids and those particles for 551 00:36:16,560 --> 00:36:17,560 example. 552 00:36:17,560 --> 00:36:21,080 There are other challenges like, you know, many of people who did dealt with, you may 553 00:36:21,080 --> 00:36:22,880 have dealt with those, the vaccines. 554 00:36:22,880 --> 00:36:26,480 You need those special fridges to keep them minus 80 degrees Celsius, right? 555 00:36:26,480 --> 00:36:28,640 It was a nightmare for distribution. 556 00:36:28,640 --> 00:36:32,160 So there's solutions coming to make them more thermostable, right? 557 00:36:32,160 --> 00:36:35,960 You have vaccines that you can keep at room temperature and that affects the whole distribution 558 00:36:35,960 --> 00:36:40,480 and also ultimately how fast you can respond if something emerges and the availability 559 00:36:40,480 --> 00:36:42,840 of the drugs in your practice. 560 00:36:42,840 --> 00:36:48,320 So there's research and stability also of those vaccines going on as well. 561 00:36:48,320 --> 00:36:49,400 It's going in overdrive. 562 00:36:49,400 --> 00:36:52,560 It's very exciting to see this coming. 563 00:36:52,560 --> 00:36:57,160 And to me, the most exciting part is disease that were out of reach before like cancer 564 00:36:57,160 --> 00:36:59,480 now having options with those. 565 00:36:59,480 --> 00:37:05,140 So it's a lot of hope for patients that, you know, had few options before. 566 00:37:05,140 --> 00:37:10,040 And then I guess just for like my own knowledge because I deal with a lot of, you know, infections, 567 00:37:10,040 --> 00:37:16,440 deficiencies, transplant, is there any talk with mRNA kind of in the immune deficiency 568 00:37:16,440 --> 00:37:20,080 world or bone marrow transplant, stem cell transplant? 569 00:37:20,080 --> 00:37:26,840 Is there any discussions around bringing mRNA technologies for treatment options there? 570 00:37:26,840 --> 00:37:32,480 The intersect between messenger RNA based therapeutics or RNA therapeutics in that larger, 571 00:37:32,480 --> 00:37:38,520 but messenger RNA therapeutics in particular and the immune system is a sweet spot. 572 00:37:38,520 --> 00:37:42,400 That's where we're successful and there's going to be more and more uses there. 573 00:37:42,400 --> 00:37:44,880 I'm not an expert to precisely answer your question. 574 00:37:44,880 --> 00:37:49,000 I'm not an expert and I don't know really what's being done there. 575 00:37:49,000 --> 00:37:53,840 What I can tell you though is that of all the clinical trials, most of them with messenger 576 00:37:53,840 --> 00:37:56,840 RNAs, most of them have to do with the immune system. 577 00:37:56,840 --> 00:38:01,440 And you could have things like chronic inflammation, the chronic disease, right, that are undergoing 578 00:38:01,440 --> 00:38:03,280 autoimmunity. 579 00:38:03,280 --> 00:38:09,600 I wouldn't be surprised if there's breakthroughs there with those therapies. 580 00:38:09,600 --> 00:38:15,440 I don't know how fast it will come, but if I had a chunk of money to put on somewhere 581 00:38:15,440 --> 00:38:19,760 where it's going to move fast, it's going to be on the intercept with the immune system, 582 00:38:19,760 --> 00:38:25,880 whereas immunomodulation, you know, but also, you know, we see things like, for example, 583 00:38:25,880 --> 00:38:30,680 combinatorial treatment with immunotherapy, for example, in cancer, right, the cancer 584 00:38:30,680 --> 00:38:35,440 suppresses the immune system and you can modulate that with immunotherapies. 585 00:38:35,440 --> 00:38:40,520 So there's a synergy between messenger RNA vaccines against the answer immunotherapy. 586 00:38:40,520 --> 00:38:44,080 So you'll see those combinations of treatment in the clinic, for example. 587 00:38:44,080 --> 00:38:46,720 So that's a hot space, I would say, to do research on. 588 00:38:46,720 --> 00:38:51,120 And, Rupina, if you want to do some research, I think that would be grantable, I would say, 589 00:38:51,120 --> 00:38:52,120 in the current period. 590 00:38:52,120 --> 00:38:53,120 Yeah, no, that's fair. 591 00:38:53,120 --> 00:38:54,120 Thank you so much, Dr. Tichane. 592 00:38:54,120 --> 00:39:01,240 I think, I mean, I've learned a lot about mRNA technology and, you know, through everything 593 00:39:01,240 --> 00:39:04,960 that we've spoken about today, doing a bit of my own research as well. 594 00:39:04,960 --> 00:39:10,520 And I think this is, it's nice to see that there's novel techniques that are coming up 595 00:39:10,520 --> 00:39:16,440 and we really have a future where we're not only diagnosing diseases, but we have treatment 596 00:39:16,440 --> 00:39:19,480 options and really just a better understanding, right? 597 00:39:19,480 --> 00:39:24,720 So we have experts like yourselves that can come on and talk to us about this. 598 00:39:24,720 --> 00:39:31,360 And so I think this is very different from a few multiple decades ago, where a lot of 599 00:39:31,360 --> 00:39:36,120 this information wasn't brought out to the public, wasn't brought out to clinicians and 600 00:39:36,120 --> 00:39:38,120 other audiences. 601 00:39:38,120 --> 00:39:42,440 So thank you so much for your wealth of knowledge today. 602 00:39:42,440 --> 00:39:43,440 My pleasure. 603 00:39:43,440 --> 00:39:48,680 It's what's exciting is that this is hope that's given from knowledge. 604 00:39:48,680 --> 00:39:51,600 It's from solid knowledge, from very robust knowledge. 605 00:39:51,600 --> 00:39:58,200 So it's a pleasure to be, you know, conveying this to clinicians and the general public. 606 00:39:58,200 --> 00:39:59,200 Thank you for doing what you do. 607 00:39:59,200 --> 00:40:00,200 Oh, of course. 608 00:40:00,200 --> 00:40:01,840 Thank you for doing what you do. 609 00:40:01,840 --> 00:40:05,400 I think you make my day job easier. 610 00:40:05,400 --> 00:40:07,440 So it's perfect. 611 00:40:07,440 --> 00:40:13,320 And so I think we're definitely, I'll reach back out to you at some point, because I think 612 00:40:13,320 --> 00:40:17,640 there's a lot of future to mRNA-based methods and technology. 613 00:40:17,640 --> 00:40:20,480 I know there's going to be a lot of research in this area. 614 00:40:20,480 --> 00:40:26,720 And I know that the U and R Centre will definitely be on top of it. 615 00:40:26,720 --> 00:40:32,500 And so I think it'll be nice to discuss kind of future, what the future really holds. 616 00:40:32,500 --> 00:40:37,560 Is there anything from a last standpoint that we didn't talk about in mRNA that you were 617 00:40:37,560 --> 00:40:40,600 hoping to share with our audience today? 618 00:40:40,600 --> 00:40:46,160 I just think that what we're seeing is the beginning and that the potential is huge. 619 00:40:46,160 --> 00:40:49,400 Technology is now awake to that potential. 620 00:40:49,400 --> 00:40:57,360 And it's really a very important period to fund research in that area, basic and translational. 621 00:40:57,360 --> 00:41:03,440 And you know, the potential now is absolutely clear and all the players are awake to it. 622 00:41:03,440 --> 00:41:11,560 So I think I would like to close with an appeal for to support research, both basic discovery, 623 00:41:11,560 --> 00:41:16,720 but also translational, so that we can start mobilizing this knowledge towards people, 624 00:41:16,720 --> 00:41:19,320 patients that we need and have few options. 625 00:41:19,320 --> 00:41:21,240 So that would be my last word. 626 00:41:21,240 --> 00:41:22,960 Yeah, no, that's great. 627 00:41:22,960 --> 00:41:23,960 That's fantastic. 628 00:41:23,960 --> 00:41:29,760 Anybody who's a researcher would definitely would, I think, having support in their research 629 00:41:29,760 --> 00:41:36,560 would be important, whether it's clinical, whether it's bioengineering. 630 00:41:36,560 --> 00:41:37,560 There's so many phases. 631 00:41:37,560 --> 00:41:42,800 So, yeah, I think both engineering, basic and applied, I think both need to work in 632 00:41:42,800 --> 00:41:45,200 band and those, definitely. 633 00:41:45,200 --> 00:41:46,960 We've seen it work really well with this. 634 00:41:46,960 --> 00:41:47,960 That's fantastic. 635 00:41:47,960 --> 00:41:52,320 Well, thank you so much for your time and we look forward to future episodes. 636 00:41:52,320 --> 00:41:54,360 Thank you, Rupina. 637 00:41:54,360 --> 00:41:58,000 Thank you, Dr. Duchesne, for the discussion on this interesting topic. 638 00:41:58,000 --> 00:41:59,440 Have an episode suggestion? 639 00:41:59,440 --> 00:42:05,720 Email thecanadianbreakpoint at gmail.com and be sure to follow us on x at cabreakpoint 640 00:42:05,720 --> 00:42:06,720 for updates. 641 00:42:06,720 --> 00:42:08,960 See you again soon at the Canadian Breakpoint.