All-In Summit: Gene therapy and a new era of medicine with Dr. Nicole Paulk
发布时间 2023-09-25 23:51:22 来源
摘要
This talk was recorded live at the All-In Summit 2023 at Royce Hall on UCLA's campus in Los Angeles.
(0:00) Besties welcome Dr. Nicole Paulk to All-In Summit ‘23!
(0:59) An introduction to Gene Therapy
(2:18) Three eras of modern medicine
(4:49) Living medicines
(6:35) Congenital blindness and other rare diseases
(9:37) Gene therapy applications for broad use, including cancer
(12:00) Immunosurveillance and immunotherapy
(14:44) Brain cancer test
(16:34) DEC2 mutation to reduce the need for sleep
(17:45) Gene therapy for people living on Mars
(18:40) Bestie Q&A: FDA hurdles and aging as a disease state
(21:16) Biotech’s valley of death
(23:52) Night vision and other human enhancements
(26:32) Fundraising
Follow Nicole:
https://twitter.com/Nicole_Paulk
Follow the besties:
https://twitter.com/chamath
https://linktr.ee/calacanis
https://twitter.com/DavidSacks
https://twitter.com/friedberg
Follow the pod:
https://twitter.com/theallinpod
https://linktr.ee/allinpodcast
Intro Music Credit:
https://rb.gy/tppkzl
https://twitter.com/yung_spielburg
Intro Video Credit:
https://twitter.com/TheZachEffect
Relevant links:
https://twitter.com/SirenBio
https://sirenbiotechnology.com/
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中英文字稿 
Next up is Nicole Paul. I'm really excited for this talk. I think you guys will find a lot of optimism in where technology is playing out in in biology and bioengineering to cure fundamental human disease. For nearly 20 years, she's been developing next-generation AAV platforms for gene repair, gene transfer, and gene editing. And she's directed evolution for novel engineered capsids and comparative multiomic approaches to interrogate translational AAV biology. She's gonna share a little bit about her work with her startup Siren Biotechnology, which came out of stealth last year. Please join me in welcoming Dr. Paulk to the stage.
接下来是Nicole Paul。我对这次演讲感到非常兴奋。我认为你们会在技术在生物学和生物工程中的应用方面找到很多乐观主义，来治愈根本性的人类疾病。她已经从事开发下一代AAV平台用于基因修复、基因转移和基因编辑近20年。她通过定向进化研究新型工程包衣蛋白质和比较多组学方法来探索AAV转化生物学。她将分享一些她和她的初创公司Siren Biotechnology的工作，该公司去年保持隐秘。请大家欢迎Paulk博士上台。
We like your winter slide. All right quick show of hands, how many of you have ever even heard of the phrase gene therapy or viral gene therapy before? Oh my gosh, would you guys read Wall Street Journal in the Economist? Sorry, pretty good. Usually it's like two hands. So who the heck am I? And why am I in for talking to you about this? So like they said, my name is Dr. Nicole Paulk up until like a hot minute ago. I was a professor of viral gene therapy at UCSF in San Francisco and decided to spin out a company based off some work in my lab and I'm here to talk to you guys a little bit about using viruses as medicines.
我们喜欢你们的冬季滑梯。好的，举手表决，有多少人在以前甚至听说过基因治疗或病毒基因治疗这个词？哇哦，你们会看《华尔街日报》和《经济学人》吗？很抱歉，很好。通常只会有两只手举起来。那么我是谁呢？为什么我要和你们谈论这个？正如他们所说的，我的名字是尼科尔·保尔克博士。就在一会儿之前，我还是旧金山加利福尼亚大学的病毒基因治疗教授，后来决定根据实验室的一些研究成果创办一家公司。我在这里与大家谈一谈利用病毒作为药物的一些事情。
So what is gene therapy? Broadly speaking, this is using viruses as medicines. So historically we have used these to treat single gene genetic disorders, but we can use these much more broadly now and I'll share a little bit about that. But historically we've used these when you were born either missing a gene in your genome or you had a mutation in a particular gene in your genome and all you needed in order to be completely healthy was to have a functional copy of that gene given back to you or to have the particular mutation in that gene corrected and restored for you and we can do all of these with viruses. And so if that sounds a little bit crazy and a little bit new and a little bit revolutionary, it's because it is. We're kind of quite literally living through one of the most recent and kind of newest eras of modern medicine.
那么基因疗法是什么呢？广义上说，它是利用病毒作为药物使用的方法。所以在历史上，我们一直使用它来治疗单基因遗传疾病，但现在我们可以更广泛地使用它，并且我会稍微谈谈这方面的一些情况。在历史上，当你出生时，基因组中要么缺失了某个基因，要么某个基因发生了突变，而你只需要重新获得一个功能正常的该基因副本，或者修复和恢复其中的突变，就可以完全健康。而这些都可以通过病毒来实现。所以如果听起来有点疯狂、新奇和革命性，那是因为它确实如此。我们实际上正处于现代医学最近和最新的时代之一。
And so in order to talk about where we are, we kind of need to understand where we came from. So nearly every one of you in this room, this first era of modern medicine started probably with your either your parents or your grandparents. This is with chemical medicines. This is when we realized that, gosh, every time I have a stomachache I can go eat this one particular leaf from a tree and when I eat that leaf I feel much better and then the scientists realized well we don't have to eat the leaf. We could isolate the chemical compound that comes from that leaf and then we could produce that in mass synthetically in large vats in the lab and that way we don't have to all go outside and eat and eat leaves all the time. And so the advent of chemical medicines and realizing that we could isolate these and synthesize these in mass was an absolute transformation. This is nearly every drug you've ever taken in your life. These are all the pills you can go find at your local pharmacy, particularly the ones that are over the counter. And so this is the vast majority of medicines you've ever taken in your entire life.
因此，为了谈论我们现在所处的位置，我们需要了解我们从哪里来。所以你们在座的几乎每一个人，现代医学的第一个时代可能是从你们的父母或者祖父母那里开始的。这个时代是化学药物的时代。这个时代我们意识到，每当我胃痛时，我可以吃一片来自某棵树上的特定树叶，吃了那片树叶我会感觉好多了。然后科学家们意识到，我们不需要吃树叶。我们可以分离出那片树叶中的化学物质，然后在实验室里大规模地合成它们，这样我们就不必一直外出吃树叶了。因此，化学药物的出现以及意识到我们可以分离并大规模合成它们是一个绝对的转变。这几乎是你一生中吃过的所有药物。这些都是你可以在你当地的药房找到的药丸，特别是非处方药。因此，这是你一生中使用的绝大部分药物。
And the way these chemical medicines work, right? You take that pillow, you swallow it, it goes into your stomach, it gets dissolved by the acids in your stomach, it then gets absorbed into the bloodstream in your GI tract and then goes throughout your entire body and it will bind to and affect kind of either the shape or the function or the ability of various proteins in your body in a way that's useful to reduce your symptoms. And so then in the next kind of era of medicine we had the brilliant idea, well, let's just cut out the middleman. Let's not give you a chemical that alters the shape or function of a protein. Let's just give you the protein. Let's advance to protein medicines. And let's now take a protein that has the particular shape in the function that you might need in order to provide some kind of therapeutic benefit for the disease state that you have and give you that as a drug. And so that's kind of been the next kind of most recent wave of modern medicine. And so this is things like enzyme treatments and antibody therapies.
这些化学药物的工作方式是这样的，对吧？你拿起那个药丸，吞下去，它进入你的胃，被胃酸溶解，然后从你的胃肠道吸收进入血液，并在你的整个身体中结合并影响各种蛋白质的形状、功能或能力，从而有助于减轻你的症状。所以在下一个医学时代，我们有了一个绝妙的想法，嗯，为什么不直接切掉中间人呢？我们不给你一种改变蛋白质形状或功能的化学物质，而是直接给你蛋白质。让我们进入蛋白质药物的领域。现在我们可以选择一种拥有特定形状和功能的蛋白质，以便为你所患疾病提供一些治疗方面的益处，并将其作为药物给予你。因此，这就是现代医学中最近的一波发展。这类治疗方法包括酶治疗和抗体疗法。
Many of you in the room have probably heard of the most successful drug of all time. Anyone know what it is? Anyone want to shout out a guess? What's the most successful drug of all time? That's raised the most money. It's not my agro, guys. Humira, someone said it. So this is an antibody that's used to treat a particular form of arthritis. This antibody sells on average a little over $21 billion worth of just that drug every single year and has been the most successful drug for the last 20 years. This is what we call a blockbuster. This is what everyone is shooting for in their portfolio as a blockbuster drug. And it's an antibody.
在座的很多人可能听说过有史以来最成功的药物。有人知道是什么吗？有人想猜一猜吗？有史以来获得最多利润的药物是什么？这与我无关，伙计们。有人说是Humira。所以这是一种用于治疗特定形式关节炎的抗体。每年仅这种药物的销售额就超过了210亿美元，并且在过去20年里一直是最成功的药物。这就是我们所谓的巨型卖家。这就是每个人在他们的投资组合中都努力追求的巨型卖家药物。而且它是一种抗体。
But now we're entering kind of this newest third modern form of medicine, which is what we call living medicines. This is using things like viruses, bacteria, cells, things that are quote unquote, alive that we can now use to go in and impart changes in your body.
但是现在我们正在进入一种全新的第三种现代医学形式，我们称之为活体药物。这种医学利用病毒、细菌、细胞等被认为是“活着的”物质，可以用于对你的身体进行改变。
Why would we do that? Well, both chemical medicines and protein medicines, we typically either give orally or we give intravenously, which means they're going to go throughout your entire body. But in some cases, we don't want a drug to go to your entire body. Like, for example, when you take chemo, boy, you feel like trash, right? It's because it's also affecting healthy cells in your body. So sometimes we want the medicine to only go into a simple place in your body or a single place. So that way you only experience the therapeutic effect in a single location.
为什么我们要这样做呢？其实，化学药物和蛋白质药物通常是通过口服或静脉注射给予的，这意味着它们会在你整个身体中传播。但在某些情况下，我们不希望药物进入你的整个身体。比如，当你接受化疗时，你会感觉非常糟糕，对吗？这是因为它也会影响你体内的健康细胞。所以有时候，我们希望药物只进入身体中的一个简单或单一的位置。这样你只会在一个地方体验到治疗效果。
The other really cool thing we can do with things like viruses and cells is we can engineer, I know many of you here, like tech or tech adjacent, we can engineer in logic circuits. So we can add things like if, then, or and, and all these types of kind of Boolean logic, we can engineer those circuits into viruses and cells and have them perform those same types of decisions within your body. Like, if you experience this, release the drug. If you experience this, don't. So you can engineer in these types of circuits in order to get this really, really precise delivery of any particular medicine that you're interested in delivering.
我们还可以利用病毒和细胞等物质来进行一项非常酷的事情，那就是我们可以通过工程手段，我知道这里有许多喜欢科技或与科技相关的人，我们可以在逻辑电路中进行工程设计。因此，我们可以添加if（如果）、then（那么）、or（或）和所有这些布尔逻辑的类型，并将这些电路工程化到病毒和细胞中，让它们在你的身体内做出这些相同类型的决策。比如，如果你感受到这种情况，就释放药物。如果你感受到这种情况，就不要释放。因此，你可以在其中工程化这些类型的电路，以实现对所需药物的非常精确的输送。
And you can package almost anything in a virus. And so a really common misconception is that all viruses are bad for you. All viruses make you sick. Couldn't be farther from the truth. The vast majority of viruses on the planet are very good at getting inside of you, but very few of them make you sick. I bet most of you can't name more than 20 viruses. And all the viruses you can name are viruses that make you sick, like measles, mumps, polio, smallpoxes, types of things. We only know of them because we studied them because they make us sick. But the vast majority of the viruses on the planet can actually kind of be considered our allies. They're tools that we can use that don't make us sick, but they're still very good at getting inside of us, that we can use to deliver all kinds of medicines.
你几乎可以将任何东西包装成病毒。因此，一个常见的误解是认为所有的病毒都对你有害。所有的病毒都会使你生病。这是完全错误的观念。地球上绝大多数的病毒都很擅长侵入你的体内，但其中很少有病毒会让你生病。我敢打赌大多数人都无法说出超过20种病毒的名字。而你能想到的所有病毒都是那些让你生病的病毒，比如麻疹、腮腺炎、小儿麻痹症、天花等等。我们只知道它们是因为我们研究了它们，因为它们让我们生病。但是地球上绝大多数的病毒实际上可以被认为是我们的盟友。它们是我们可以利用的工具，不会让我们生病，但是它们很擅长进入我们的体内，我们可以用它们来传递各种药物。
So all of this is talk. Much more fun to look at is an actual video of this in action. And so what I'm going to show you on this screen is a patient from a clinical trial, from a patient that has a rare form of inherited genetic blindness. This is a disease called Lieber's Congenital Amorosis. These patients are born basically medically blind. They cannot see at birth.
所以这只是谈论而已。看实际视频会更有趣。我将在屏幕上向你展示一位参与临床试验的患者，他患有一种罕见的遗传性视力丧失疾病。这种疾病被称为利贝尔先天性遗传性失明症。这些患者从出生开始就基本上是医学上的失明。他们在出生时无法看见。
And you're going to see two videos. The one on the left is going to be this patient pretreatment attempting to navigate a maze. You can see that maze on the floor at very, very low light. So the reason that this looks very yellow is because it's taken at one luminal unit or low light. All of us have much poorer visual acuity, a low light, then we do it highlight. So it's not that this video was taken in 1985. It was just in very, very low light. That's why it looks yellow.
你将看到两个视频。左边的那个视频是患者在治疗前尝试穿越迷宫。你可以看到地板上的迷宫，但是非常非常暗。所以这个视频看起来很黄是因为在一单位亮度或者说非常暗的光线下拍摄的。我们所有人在低光照下的视力都比在高亮度下差得多。所以这不是因为这个视频是在1985年拍摄的，而是因为光线非常暗，所以它看起来是黄色的。
So I'm actually going to start that video and I'll kind of talk over this patient while they're going. So this patient's medically blind. They cannot see the arrows on the ground that they're being told to navigate, nor can they see the little obstacles that they're being told like you should step over. So they're feeling for them with their feet, just like you would if you were blind and you didn't have your walking stick. You would just kind of feel in front of you to see what was there so that you wouldn't manage to trip and fall. So I'm not actually going to show you this entire video because it took this poor patient 214 seconds to attempt this navigate, this 8 foot, 8 foot by 8 foot maze. And all this patient needed, they were missing a single protein in the back of their eye. All they needed was a single viral infusion for that virus to express a single protein that that patient was missing in their eye.
所以实际上，我要开始播放这个视频，并且在病人进行过程中进行解说。这位病人患有医学上的失明。他们看不到地上的箭头，也看不到被告知要绕过的小障碍物。所以他们用脚去感觉，就像你如果是盲人而没有拐杖的话，你会摸索前方来确定不会绊倒摔倒。我实际上不会给你展示整个视频，因为这位可怜的病人花了214秒尝试通过这个8英尺乘8英尺的迷宫。而这位病人所需要的只是在眼睛后方缺失一种蛋白质。他们所需要的只是注入一种病毒，使其表达病人眼睛中缺失的一种蛋白质。
And this is that exact same patient. Again, this was a 10 year old, just one year after treatment. They would have been able to do this within seven days though. So they have absolutely perfect vision. So we're able to keep the human blindness. This same young patient has now gone on to get their driver's license. They are walking, quite literally, they are walking amongst us, leading a completely normal life.
这就是同一个患者。再次强调，他在治疗一年后才10岁。虽然在七天内他们就能做到这一点。所以他们拥有完美的视力。我们能够挽救人类的失明。同一个年轻的患者已经获得了驾驶执照。他们正步行在我们中间，过着完全正常的生活。
So this feels crazy and revolutionary like, oh my gosh, I hadn't heard about this. When is this coming for the rest of us in all of our indications? Soon. Where are we now? This is a one year old slide. The next prospectus from Wells Fargo is expected to come out any day now. I was hoping it would come out before this talk, but it didn't.
这感觉疯狂而具有革命性，哦天啊，我从没听说过这个。这些对于我们全方位的适用将会在什么时候实现？很快。我们现在处于什么阶段？这是一张一年前的幻灯片。下一份富国银行的招股说明书预计将于近日发布。我原本希望它能在这次演讲之前发布，但没能实现。
But this is the annual prospectus they put out every year. Kind of the advancement of these gene therapy companies, they do this for every industry, but this is for gene therapy. So this is all of the logos of all of the companies that are working in gene therapy for various diseases. The outer rings are kind of the earliest stages of development, those phase one, phase two trials. And as you move towards the center, towards the bullseye, that's when you're FDA approved and you can sell your drug for hopefully $21 billion a year and be a blockbuster.
但这是他们每年发布的年度招股说明书。这是基因治疗公司的发展情况，他们为每个行业都这样做，而这是关于基因治疗的。因此，这些都是处理各种疾病的基因治疗公司的所有标志。外围是最早期的发展阶段，即第一和第二阶段的试验。当你朝着中心移动，接近中心靶心时，那就是当你获得FDA批准并能以每年210亿美元的价格销售你的药物并成为一款畅销品的时候。
But as you can see, right, there is a wave of gene therapies coming for even those few of you who didn't raise your hand earlier that you had ever heard of gene therapy before. I promise you, in your lifetime, no matter how old any of you are in this audience, in your lifetime, you are going to receive a viral gene therapy's medicine.
但正如你们所看到的，对于那些之前从未听说过基因治疗的少数人来说，也将有一波基因疗法的浪潮到来。我向你们保证，在你们的一生中，无论你们在观众中年龄有多大，你们都将接受一种病毒基因疗法的药物。
So there's a particular virus, Dave mentioned it earlier that I like to work on. This virus called AV. And it's typically used like we were mentioning before to treat rare genetic disorders. Some of the disorders that we've been able to cure are the ones shown here on this slide. And again, we've typically only done rare single gene disorders. And in my lab at UCSF and now at the company, we wanted to ask a little bit bolder question. Typically, we've only used these to treat rare genetic disorders. Could we use these to treat other indication spaces? Ones with many more patients where the need is much greater and the benefit to humanity would be much more.
所以有一种特殊的病毒，戴夫之前提到过，我很喜欢研究它。这种病毒被称为AV。通常它被用来治疗罕见的遗传疾病，就像我们之前提到的那样。我们已经成功治愈的一些疾病在这张幻灯片上展示出来了。再次强调，我们通常只治疗罕见的单基因疾病。在我在UCSF的实验室以及现在在公司里，我们想提出一个更大胆的问题。通常，我们只使用这些来治疗罕见的遗传疾病。我们能否将其用于治疗其他疾病领域？这些领域有更多的患者，需求更迫切，对人类的利益也更大。
So we wanted to ask a rather audacious question. Rather than having a virus that might cause cancer, could you use a virus to cure cancer? Could you actually use a virus as a medicine that could be used to treat cancer? So we've been working on this for the last seven years to try to go against conventional gene therapy.
所以我们想要问一个相当大胆的问题。与其说是有可能引起癌症的病毒，能否利用病毒来治愈癌症呢？你是否真的可以使用病毒作为一种可以用来治疗癌症的药物？因此，我们在过去的七年中一直在努力与常规基因治疗背道而驰。
So every gene therapy on the planet, all the ones on that bull's eye just showed you on the last slide, whether they're from academia, industry, big pharma, doesn't matter. Every one of those is bespoke and personalized for a single indication. So that virus that you make can only be used to treat that one disease and no other disease. And every one of those viruses takes about 10 to 15 years to develop. This is very time intensive. Usually on average, about two to three billion dollars. So maybe not necessarily as expensive as the gentleman who just left the stage, but a very, very expensive technology nonetheless. And typically treat very, very small patient populations. The definition of a rare disease in the United States is anything that occurs in fewer than 200,000 patients a year. But most of those gene therapies are going after indications with like 100 patients, 200 patients, so very, very rare disorders.
所以，地球上的每种基因疗法，无论是来自学术界、行业界还是大型制药公司，都是量身定制并个性化针对单一病症的。因此，你制造的病毒只能用于治疗那一个疾病，而不能用于治疗其他疾病。而且，这些病毒的开发需要大约10到15年的时间。这是非常耗时的过程。平均而言，需要约20到30亿美元的资金。也许并没有刚刚离开台上的那位先生引用的那么昂贵，但无论如何都是一项非常昂贵的技术。而且，通常只能治疗非常小规模的患者群体。在美国，罕见病的定义是每年发生在少于20万患者身上的疾病。但是，大多数基因疗法都针对只有100名患者、200名患者这样非常罕见的病症。
And so we wanted to go after something that would help much more of humanity. And so we wanted to ask the question, could we make a single gene therapy that could be used to treat millions of patients across a variety of indication spaces, things like cancer, where they're often very similar to one another? Could you make a universal gene therapy? Is that even a thing? And so we wanted to kind of set out on a fairly audacious project to not only bring viral gene therapy to the oncology world, but to blend it with one of the newest forms of oncology, which is this idea, this concept of immunotherapy. Many of you have maybe even heard of this before.
因此，我们想要追求一些能够更好地帮助人类的事情。因此，我们想要问一个问题，我们是否能够制造一种单一基因疗法，用于治疗数百万患者，涵盖各种情况，比如癌症，在这些情况下它们通常非常相似？你能否制造一种通用基因疗法？这种事情真的存在吗？因此，我们希望开始一个相当大胆的计划，不仅将病毒基因疗法引入肿瘤学领域，而且将其与最新形式的肿瘤学相结合，即这种概念，免疫疗法。你们中的许多人可能甚至听说过这个概念。
There's a variety of different ways you can accomplish this. They all essentially work the same way, where they retrain your immune system to fight cancer. And I'm using that word, retrain very purposefully. Every single one of you in this audience has a tumor. You've had a tumor every single day of your life. It's usually a single cell. You often have many of them throughout your body. Your immune system is doing what's called background cancer immunosurveillance. Your immune system is circulating throughout your body every single day, and it's actually able to detect and find and sniff out where those tumors are and get rid of them while they are, while they are still single cells.
有各种不同的方法可以实现这一点。它们本质上都以相同的方式工作，即重新训练您的免疫系统来对抗癌症。而我之所以有意地使用“重新训练”这个词。在座的每一个人每天都有一个肿瘤。通常是一个单个细胞。在您的身体中通常会有很多这样的细胞。您的免疫系统正在进行所谓的背景癌症免疫监测。您的免疫系统每天在体内循环，它实际上能够检测、发现和察觉到这些肿瘤的存在，并在它们仍然是单个细胞时消灭它们。
How do they do this? It's a single tumor cell, wherever it is in your body. It sends out little chemical cues to the local environment as well as the immune system, and the healthy cells that surround that tumor are also able to detect something weird about that guy. And they'll send a little message over to the immune system and they'll be like, come over and do an investigation. Check him out.
他们是如何做到这一点的呢？无论体内的哪个部位，它只是一个单个的肿瘤细胞。它会向局部环境和免疫系统发出一些微小的化学信号，周围健康的细胞也能察觉到这个肿瘤的异常之处。然后它们会向免疫系统发送一条小消息，就像是说：“过来调查一下吧，看看这个家伙怎么回事。”
What's up with him? Your immune system will come over, sniff it out and be like, yeah, I agree. Something's up with him. And they'll kill that cell. And this is happening all the time throughout your entire body. It's our immune system right now. Today. Your immune system knows how to fight cancer. It's exquisite at it. So how in the heck do you ever get a baseball-sized tumor? How does that happen? It happens because that individual tumor cell through a variety of different mechanisms, there are many ways this happens, but typically somehow, through one or two mechanisms, it will end up basically randomly generating a mutation that will give it essentially an invisibility cloak. That invisibility cloak makes it so that those neighboring healthy cells can't detect that something's up with it, so they don't send a message to the immune system. And because it's a little bit invisible, your immune system also can't just randomly swim by and detect it and see that something's wrong. And so because it can't be seen, it can't be destroyed, and so then it starts to grow and become your big baseball-sized mass, and then you become symptomatic, right? And then you go to the doctor.
他怎么了？你的免疫系统会出现并嗅探出问题，然后说，是的，我同意。他有问题。然后它们会杀死那个细胞。这种情况在你全身都会发生，就是我们的免疫系统。就在今天。你的免疫系统知道如何对抗癌症，擅长这个。那么，到底如何会有一个棒球大小的肿瘤呢？这是怎么发生的？它发生是因为那个单个的肿瘤细胞通过各种机制，有很多种方式，但通常通过一两种机制，它最终会随机产生一个突变，使其基本上具备隐形斗篷。这个隐形斗篷使得周围的健康细胞无法察觉它是否有问题，所以它们不会向免疫系统发送信号。而且由于它有点隐形，你的免疫系统也无法随机游过去检测并发现有问题。因此，由于它无法被看到，也就无法被摧毁，然后它开始生长并成为一个巨大的棒球大小的肿块，然后你会出现症状，对吧？然后你就去看医生。
But you can retrain your immune system to be able to see that invisible tumor, and if you can do that with immunotherapy, then now you've got a way to destroy a tumor that doesn't involve chemo, that doesn't involve radiation, that basically uses your own immune system to fight cancers. And so we wanted to blend the power of virology and therapy and the precision delivery and kind of those logic circuits around like, do this when you experience this, these types of things with immunotherapy to see if we couldn't do something important in the cancer space.
但是你可以重新训练你的免疫系统，让它能够察觉那些看不见的肿瘤。如果你能通过免疫疗法做到这一点，那么现在你就有一种不需要化疗，不需要放射治疗的方式来消灭肿瘤，而基本上是利用你自己的免疫系统来抗击癌症。因此，我们希望将病毒学和治疗的力量以及精确的传递技术结合起来，并搭建逻辑电路，例如在经历某种情况时执行某种操作，利用免疫疗法来看看我们是否能在癌症领域做出重要的贡献。
And so we developed a platform, a variety of different universal gene therapies in my lab at UCSF and spun those out into the company, and the name of the company is actually based off the mechanism of action here. So we can take these viruses, have them deliver a variety of different kind of cancer announcing payloads that will announce to immune system. The cancer is here, and so that way both the cancer cells, as well as the neighboring cells, will basically set off the fire alarm, pull the siren, and let the immune system know this is where we're going to be able to see that. So we're going to be able to see that the immune system know this is where the tumor is coming and fight it, and you'll have these three different waves of tumor killing that can happen both with your innate and your adaptive immune system.
因此，我们在UCSF的实验室中开发了一个平台，一系列不同的通用基因疗法，并将其拆分为一家新公司，并且该公司的名称实际上是根据这里的作用机制而命名的。因此，我们可以利用这些病毒，让它们传递各种不同类型的癌症通知负载，以通知免疫系统癌症已到达。癌症已到达，这样癌细胞和周围细胞都会触发火警，拉响警报器，让免疫系统知道我们将能够看到这一点。因此，我们将能够看到免疫系统知道肿瘤即将到来并与之抗争，您将能够体验到您的先天和适应性免疫系统对肿瘤的三种不同阶段的杀伤作用。
So while we were still at UCSF, we were like, okay, we have this really cool idea, we want to try this, but we're agnostic to any particular cancer type because again, we weren't an oncology lab, we were a viral gene therapy lab. So we went over to our colleagues at the cancer center and we're like, what's the gnarliest cancer? What's the one that nothing works? And then they said, go after brain cancer. So we decided we'd start collaborating with folks at UCSF to determine a brain cancer kind of path. But how do you test a drug in order to make sure it works on human brain cancer when you can't test it yet on humans because the FDA wants you to have a data package before you go up for your clinical trial. So the way you test it is you actually make mice with human brain cancer.
在我们还在UCSF的时候，我们有一个非常棒的想法，想要尝试一下。但是我们对于特定的癌症类型没有任何偏好，因为我们不是一个肿瘤学实验室，而是一个病毒基因疗法实验室。所以我们去了癌症中心的同事那里，问他们：哪种最难治的癌症？哪种癌症治疗都无效？然后他们告诉我们，去研究脑癌。于是我们决定开始与UCSF的人合作，找出一种脑癌的疗法。但是如何测试一种药物，以确保它对人类脑癌有效，因为在你进行临床试验之前，FDA要求你提供数据包。所以你可以做的测试是制造带有人类脑癌的小鼠。
So you can take brain cancer samples from humans, from biopsies and resections, transplant those into mice, they'll grow a mini human brain tumor, you can come in and now treat them with your human drug, not your mouse drug, your human drug to test if it works, and look to see whether or not you get a response. And this is a quick little sample from three mice from a treatment group where you can see those big colored blobs of the tumors in the brains of these mice. This is live, non-invasive, bioluminescent imaging, where the control treated mice that receive either a control virus, or just receive sterile saline, have massive tumors in mice dive versus the mice that have been treated with our virus, where we can completely eliminate these tumors. As you would imagine, if you can eliminate the tumors with imaging, that might just correspond to improvements in life expectancy.
因此，您可以从人的脑癌样本，从活检和切除术中提取样本，将它们移植到小鼠体内，它们将会生长出一个迷你人类脑肿瘤，您可以使用人类药物而不是鼠标药物对其进行治疗，以测试其是否有效，并观察是否有反应。这是来自治疗组的三只小鼠的一个快速小样本，您可以在这些小鼠的大脑中看到那些大的有色肿瘤斑块。这是活体、非侵入性的生物发光成像，对于接受控制病毒或纯净生理盐水的对照组小鼠，它们的肿瘤大量增长，而与我们的病毒治疗小鼠相比，我们可以完全消除这些肿瘤。正如您所想象的，如果您可以通过成像消除肿瘤，这可能对寿命有所改善。
This is the one and only graph that I'm showing you. Very simple. It's a survival curve. The line is vertical. You died. The line is horizontal. You lived. So we can massively improve the lifespans of these animals and for all intents and purposes, cure these mice of brain cancer. And we're queuing up for a clinical trial in 2025. So we're excited to start our clinical trial in 2025.
这是唯一一个我要展示给你们的图表，非常简单。它是一条生存曲线。曲线垂直表示死亡，曲线水平表示生存。因此，我们可以大幅延长这些动物的寿命，并在所有意图上治愈这些小鼠的脑癌。我们计划在2025年进行临床试验，所以我们对于在2025年开始临床试验非常兴奋。
And very quickly, I'm going to share with you guys maybe like 15, three little 15-second vignettes on what else could we do with viruses? So we see a gentleman here sleeping. How many of you are short on sleep? Every one of you raise your hands. Come on.
很快，我要和大家分享大约15个15秒的小剪辑，看看我们还可以用病毒做什么事情。我们看到这里有一个先生正在睡觉。有多少人睡眠不足？举起你们的手，所有人都举起来。来吧。
So there is a rare mutation that happens in patients. These are people walking amongst us. We have a mutation in a gene called DEC2. These patients, again, single mutation, single gene. These patients only need four hours of sleep a night to be completely rested the same way that we have the need for eight to nine hours of sleep a night. You interested in getting this gene therapy? We could do this today. We haven't yet, but we could do this today.
所以，在患者中发生了一种罕见的突变。这些人就在我们中间走动着。我们的基因中发生了一种名为DEC2的突变。这些患者只需要每晚四个小时的睡眠就可以完全恢复，就像我们每晚都需要八到九个小时的睡眠一样。你对接受这种基因疗法感兴趣吗？我们今天就可以做到。虽然我们还没有，但我们今天就可以做到。
Another example, most of us in the room, pretty probably interested in longevity. We could use viruses to regenerate the tissue in all of your joints, maybe get rid of things like cellulite, viruses, brain fog, all these types of things. This is probably a few more years out. We're probably five to ten years out on being ready to do this, but this is absolutely coming in your lifetime. You could get a rejuvenation gene therapy. You really want to talk far out? We could talk about maybe 30 years from now. We could absolutely engineer humanity to withstand life in much more drastically harsh environments. So we could alter your skin color to be able to reflect more UV light so you wouldn't get as much damage if perhaps say you were living on Mars. We could engineer the cells in your gut and bacteria that live in your gut to be able to metabolize foods that are more easily grown on a Martian environment and these types of things. So really, your imagination is the limit, so could we enhance human potential? We absolutely can. It's just a matter of are you interested in when? So happy to discuss the future. These are exciting times.
另一个例子，我们房间里的大多数人，很可能对长寿感兴趣。我们可以利用病毒来再生你所有关节的组织，也许可以消除类似脂肪团、病毒、脑雾等问题。这可能还需要几年的时间。我们可能还需要五到十年的准备才能实现这一点，但这肯定会在你的一生中出现。你可以接受延年益寿的基因疗法。如果想要讨论更远的未来？我们可以谈论30年后的事情。我们完全可以改造人类，使其能够在更加恶劣的环境中生存。所以我们可以改变你的皮肤颜色以便能够反射更多紫外线，这样在火星上生活时就不会受到太多伤害。我们可以改变你肠道中的细胞和居住在肠道中的细菌，使其能够代谢在火星环境中更容易生长的食物等等。所以说，你的想象力是唯一的限制，所以我们能够提升人类的潜力吗？当然可以。问题只是你是否感兴趣。很高兴讨论未来。这是令人兴奋的时代。
Can you just help everyone understand the timing and the regulatory hurdles? Viral gene therapy had a moment where there were setbacks and just share that with everyone, how this technology has been held back, how it's progressing now, and what timelines generally look like and how it's going to bring these breakthroughs to market.
你可以帮大家理解一下时机和法规障碍吗？病毒基因治疗曾经遇到了挫折，可以与大家分享一下这项技术曾经受到的阻碍，它现在的进展情况以及一般的时间表，以及它将如何将这些突破带入市场。
Absolutely. So today, you were to start a brand new gene therapy company called SIRN Biotechnology or anything else. You wanted to develop a viral gene therapy and you wanted to get to clinic. You're still probably looking for that first program in a 10-15 year mark. It's not because it's going to take you that long to run the clinical trials. It's not going to take you that long to grow up the vats of the drug. It's mostly going to be a regulatory timeline.
当然。所以今天，你要开始一个全新的基因治疗公司，名叫SIRN生物技术或其他任何名称。你想开发一种病毒基因治疗，并希望能够进入临床阶段。你可能仍在寻找第一个在10-15年内完成的项目。这不是因为进行临床试验需要那么长的时间，也不会花费那么长的时间来培养药物。主要是因为有一个监管的时间表。
So in between each one of these clinical trials, even before you do your very first ones, we're ready today. We could start our brain cancer clinical trial today, but we're looking at 18 months of paperwork in order to file to do that first phase one, and then you need to do your data readouts. In between each one of those trials, there's this kind of massive amount of paperwork that goes in front of the FDA that needs to be reviewed, and there's back and forths.
所以在每个临床试验之间，甚至在进行第一个临床试验之前，我们今天就已经准备好了。我们可以立即开始我们的脑癌临床试验，但要申请进行第一阶段的资料需要18个月的文件工作，然后还需要进行数据分析。在每个试验之间，会有大量的文件需要提交给FDA进行审查，并且需要来回沟通。
So the regulatory hurdles, both from if you weren't even doing anything really drastic like those last three vignettes that I talked about, is still going to be 10-15 years. But if you wanted to propose something like the sleep one that I mentioned that I think we'd all, I'm certainly interested in, there you're probably looking at an ethical review board and whether or not they let you do something like that, because that's not a disease. So fun fact, the FDA only lets you queue up clinical trials to test drugs that are for diseases. But aging is not a disease state. Wanting to sleep fewer hours is not a disease state. Insomnia is. But wanting to just sleep fewer hours and be fully rested is not a disease state.
因此，无论你是否像我提到的那三个案例那样没有采取任何真正激进的措施，监管障碍仍然需要花费10-15年的时间。但是，如果你想提出像我之前提到的那个关于睡眠的想法，我确实很感兴趣，那么你可能需要经过一个伦理审查委员会的审核，看他们是否允许你做这样的事情，因为这不是一种疾病。有趣的是，美国食品药品监督管理局（FDA）只允许你排队进行针对疾病测试的临床试验。但是衰老并不是一种疾病状态。想要减少睡眠时间并且保持完全休息是不属于疾病状态的。失眠才是。但只是想要减少睡眠时间并且保持完全休息不属于疾病状态。
So we kind of have to get to this moment where does the FDA start changing their definition of disease? Do we have a new regulatory body who will review these types of things that are more like augmentations and enhancements? How are we going to grapple with this as a society? Are we okay with this?
所以我们有点必须达到这一刻，那就是美国食品药品监督管理局开始改变他们对疾病的定义？我们是否有一个新的监管机构来审查这些更像是改良和增强的事物？我们将如何面对这个社会问题？我们对此是否满意？
And let me just ask one more question. It's a great question you posed because there is increasing consensus that maybe we should think about aging itself as a disease, obviously, and that there's a lot of approaches now to addressing that.
让我再提出一个问题。你提出的问题非常好，因为现在越来越多的人意识到，也许我们应该把衰老本身看作是一种疾病，并且有很多方法可以应对衰老问题。
What about the other challenges to completing the research and the trials and scalability? What are the bottlenecks? I've talked on our show about CAR-T therapy and the challenge in getting manufacturing scaled up to treat enough patients each year. Even though the technology is here, it's FDA approved, those drugs are in market, we just can't make enough. And I've heard a lot about lentivirus production and all these other kind of viral vectors being 18-month delay, super bottleneck.
完成研究、试验和扩展方面的其他挑战是什么？有哪些瓶颈存在？我在我们的节目中谈过CAR-T疗法，以及在使生产规模化以每年治疗足够患者方面面临的挑战。尽管该技术已经存在，并且已经获得了FDA批准，这些药物也在市场上，但我们仍然无法生产足够数量。我听说过许多关于延维持病毒（lentivirus）生产以及各种病毒载体的18个月延误，成为严重的瓶颈。
How bottleneck are we in being able to do the research that you guys are doing and ultimately to get these products to market and make enough of the stuff to treat patients?
我们在进行你们正在进行的研究以及最终将这些产品推向市场并生产足够的物品来治疗患者方面遇到了多大的瓶颈？
So the single biggest bottleneck is actually not technological at all. It's financial. It's access to capital. So these are, like I said, very, very capital intensive. The average viral gene therapy is about two to three billion dollars. So it's about three times more than making one of those chemical medicines. Some of that has to do with time, how long that process takes. Every year your company is operating. That GNA, ooh, expensive. It adds up really fast. And so some of this is just access to capital. And there's any company, every one of us in this room has a company. There's, depending on your sector, there's a valley of death.
For some of you, it's a very, very early stage. For some of you, it's a little bit more later stage, but there's a valley of death where you just can't access capital before you hit this big de-risking milestone where the bigger checks will come in and private equity and those types of groups and crossover funds in your IPO. So there's a valley of death for many of these early stage companies where, usually either after your seed stage or your series A, but before you've got clinical trial readouts where people are very nervous to give you a really big check. So that's certainly the biggest hurdle right now and why you see many companies going under across the biotech space regardless of if they're cell and gene therapies.
所以，目前最大的瓶颈实际上并不是技术上的问题，而是资金问题。也就是资金的获取。就像我说的，这些项目非常依赖资金。平均而言，病毒基因治疗的成本约为20到30亿美元，这比制造化学药物要多三倍。其中一部分原因是时间，也就是整个过程需要多长时间。每年公司运营下来，总的研发、注册和审批费用都相当高昂。因此，其中一部分问题就是资金获取的问题。无论是哪个行业，每个在场的人都经营着一家公司。根据不同的行业，都会面临一个“生存危机”。对于有些人来说，这个阶段非常早；对于有些人来说，这个阶段可能稍后一些，但在这个“生存危机”期间，您无法在达到关键的“去风险”里程碑之前获得资金，而在此之后，更多的资金会通过私募股权、交叉资金和IPO进入。所以对于许多早期阶段的公司来说，经常会出现“生存危机”的问题，通常是在种子轮或A轮之后，但在临床试验结果出来之前，人们很难给你提供大额支持。所以目前最大的障碍就是这个，无论是细胞和基因疗法领域，都会出现许多公司破产。
And then from the technological side, it's still manufacturing is just like the drumbeat. Being able to manufacture these things at scale continues to be a challenge. We need folks who come from the mechanical engineering in these types of backgrounds who don't historically necessarily think of biotech as a place where they could apply their knowledge and technologies to please come over to biotech and help us make new generations of bio reactors and types of things that will allow us to produce these at scale cleanly, cheaply, and easily. And it's just not intuitive. Making chemicals at scale is something that we've been doing for 40 years. So we're really good at it. Genentech can make kilos of drugs in an afternoon with a robot, but viruses are still something like if I queue up the biggest CDMO in the world, Cadillac pharma, and ask them to make us a 5,000 liter bioreactor of virus they'll absolutely say yes, but they won't even touch it for two and a half years.
然后从技术角度来看，制造仍然像鼓点一样进行。能够大规模制造这些东西仍然是一个挑战。我们需要来自机械工程等背景的人们，他们历史上并不一定把生物技术视为他们可以应用知识和技术的地方，请过来帮助我们制造新一代的生物反应器和能够让我们以清洁、廉价和容易的方式大规模生产的东西。这并不是显而易见的。40年来，我们一直在大规模生产化学物质，所以我们在这方面非常擅长。Genentech可以在下午用机器人制造几公斤药物，但病毒仍然是一种需要时间的东西，即使我找到了世界上最大的医药合同制造组织Cadillac Pharma，要求他们为我们制造一台5000升的病毒生物反应器，他们肯定会答应，但他们不会在两年半内动手。
I wanted to double click on the concept of making life better for people who aren't sick. The Marty Seligman from the American Psychological Association actually posed this question 20 years ago and he said what we try to make, all of psychology and psychiatry is taking depressed people and anxious people and making them less depressed and anxious. What about meaning and fulfillment for people who are content? What about more joy? And so when you look at the field and it's amazing the progress you're making and thank you for doing all that work, aside from hey can we sleep less? What else is, do you talk about, wow, if we had the mandate to take healthy people and give them a gift of augmenting them, making them into superheroes almost? We're talking about X-Men mutations here. What are the fun things that you dream about that you could do for humanity? Could we all just have vision like hawks or? Oh night vision is totally possible. Night vision? Yeah, easy. Literally without the goggles. Yeah, easy. I mean a world in which we. That's just an FDA like I need the green light, but no that's easy. So okay, that feels like Professor X kind of like shit, I like it. What else you got? Keep going.
我想进一步探讨如何为身体健康的人们改善生活的概念。美国心理学协会的马蒂·塞利格曼实际上在20年前提出了这个问题，他说我们试图做的是让心理学和精神病学能够让抑郁和焦虑的人变得不那么抑郁和焦虑。那么对于那些心满意足的人来说，有关意义和满足感的问题呢？还有更多的快乐？所以当你看着这个领域的进步，实现了那么多，感谢你所做的一切工作，除了减少睡眠时间以外，你还谈论了什么，哇，如果我们有责任将健康的人打造成超级英雄，给予他们增强自身能力的礼物呢？我们在谈论X战警中的变异能力。你对能为人类做的有趣事情有什么梦想？我们能都像鹰一样拥有敏锐的视力吗？哦，夜视完全可能。夜视？是的，很容易。甚至不用佩戴护目镜。是的，很容易。我是说，一个世界，在那个世界里...这仅仅是需要 FDA 批准的问题，但这很容易。所以好吧，感觉有点像X教授那样，很喜欢。你还有什么其他的想法？继续说吧。
Night vision would be possible the ability to metabolize a food that grows perhaps in a different environment that not only you can't get any nutrients from, but you can't even absorb it so we could make it so that you could pretend soil and it tasted good. You could eat anything and not only could it taste good to you, but it could provide you all the nutrients that you need and be able to grow with much less, much less water and in the types of environments that we'll have in the future planet given the climate change challenges that we all have.
夜视能力有可能是一种能够新陈代谢一种在不同环境中生长的食物的能力。这种食物不仅你无法获取任何营养，甚至无法吸收，但我们可以将其转化为你能够模拟土壤且口感好的食物。你可以吃任何东西，不仅口感好，而且可以提供所有你所需的营养，并且可以在未来的行星上，在面临气候变化挑战的情况下，借助更少的水和更不适合的环境中生长。
As far as other augmentations, I mean there's all of the obvious beauty applications that I think all of us are already doing. Now we just be doing this with a different modality, right? There's a gene therapy company in San Diego working on male pattern baldness. There are folks working on all the wrinkles and cellulite and getting your hair color back and all of the normal beauty things that you would expect. That's absolutely coming, but as far as beyond the obvious beauty things like what other types of augmentations I think the mental health space is a huge one because it's usually a very, very simple thing. It's complex, but it's simple. They're usually missing a single receptor or a single protein somewhere in their brain and if we were just able to restore that for them in just that location and not everywhere in their body, you could restore joy. You could restore happiness, all of these types of things.
就其他增强方面而言，我指的是所有显而易见的美容应用，我认为我们都已经在做。现在我们只是用一种不同的方式做而已，对吧？圣地亚哥有一家基因治疗公司正在研究男性秃头问题。还有人在解决皱纹、脂肪和恢复头发颜色等常见的美容问题。这些都绝对会实现，但除了显而易见的美容之外，我认为心理健康领域也是一个巨大的领域，因为通常情况下它并不复杂。尽管它很复杂，但实质上很简单。他们通常只是在大脑某个地方缺失一个受体或一种蛋白质，如果我们能够在那个地方恢复它们，而不是在他们整个身体内，就能够恢复快乐。我们可以恢复幸福，以及其他各种感受。
Do you want to talk about the capital markets piece because you mentioned you need capital? Yeah, we're fundraising. Hi. Yeah. And, uh, Tamar, maybe you can help out here, but, you know, the biotech market's been decimated since November of 21 and it's really intricately linked to interest rates because of how far out you have to make a bet on a biotech company and so as a result evaluations have plummeted 80, 90 percent. In many cases, a lot of stuff's just not getting funded right now. Um, maybe Tamar, you can share your point of view on where things are headed there and, um, Nicole, maybe you can share a little bit about what the experience has been fundraising even though you have a great technology that's got some proof points. How hard is it?
你想讨论一下资本市场的问题吗？因为你提到你需要资金。是的，我们正在筹款。嗨。是的。也许Tamar在这方面可以帮忙，但是你知道，自从21年11月以来，生物技术市场遭受了严重损失，这与利率息息相关，因为你需要在一个生物技术公司上做出一个遥远的赌注，所以评估价值下降了80%到90%。在许多情况下，很多项目现在都得不到资金支持。或许Tamar你可以分享一下你对未来走势的看法，而Nicole，也许你可以分享一下你的筹款经历，尽管你们拥有一项很棒的技术并有一些证明。那有多难呢？
Well, I have a kind of a technical question, but which is just. You had to. when you picked AAV, you had to make a decision about small edits and not large edits, I guess, right? So just explain to these guys about what payloads are actually possible in AAV, and are you thinking about what happens if you actually have to go beyond 4KB and how are you going to solve that? So, sorry. Because a lot of the diseases that these guys will actually probably understand are not small snips. They're going to be large, you know, cut and paste.
嗯，我有一个技术问题，但是这只是理所当然的。选择AAV时，你必须做出关于小幅修改而不是大幅修改的决定，对吧？所以请向这些人解释一下在AAV中实际可能的有效载荷是什么，并且你是否考虑过如果需要超过4KB而需要如何解决呢？所以，抱歉。因为这些人实际上可能理解的疾病很多不是小的修剪，而是大范围的剪切和粘贴。
Two types of gene therapy. There's gene transfer gene therapy, where we give you the whole gene that you were missing, like perhaps you were missing that portion of your chromosomal birth, so that's gene transfer gene therapy. We're literally transferring a functional copy of the gene back to you.
两种基因治疗方法。第一种是基因转移基因治疗，我们会给你完整的基因，补充你所缺失的部分，比如你的染色体缺失了这部分，我们会将一个能够正常功能的基因副本转移到你的体内。
And then there's gene editing gene therapy where we go in and actually correct a mutation in place, uh, within your genome and don't give you anything extra.
然后，还有基因编辑和基因治疗，我们会进入体内实际上纠正基因突变的地方，不会给你添加任何额外物质。
So every virus on the planet has a carrying capacity. It has a size, just like a sedan, can't carry as much as a minivan. Um, and so AAV viruses, the viruses that I work on, are amongst one of the smaller viruses. So it can only package about 4.75KB. So the numbers of nucleotides that you can fit inside of it, and different viruses have larger packaging capacities and can fit more stuff, more packages inside. That's 4,700 letters of DNA. Um, and so different viruses will have different packaging capacities.
所以地球上的每种病毒都有一个携带能力。就像一辆小轿车和一辆面包车一样，它有一个大小限制，不能像面包车一样携带很多东西。嗯，所以AAV病毒，也就是我正在研究的病毒，是比较小的病毒之一。它只能携带大约4.75KB的物质。所以你可以将多少个核苷酸装入其中，不同的病毒有不同的包装能力，可以装更多的物质、更多的包裹。那就是4,700个DNA碱基。嗯，所以不同病毒的包装能力也会不同。
And so if you're doing gene transfer gene therapy where you need to provide the entire copy of the gene, you can only put in genes that will fit with all of the other regulatory elements for expression within that virus. So of all protein coding genes, since we're typically going after diseases that are influencing a protein, of all protein coding genes, 80% of those genes can fit within my virus. So actually the vast majority of genetic diseases can be treated with AAV gene therapy, with gene transfer gene therapy.
因此，如果你正在进行基因转移基因治疗，需要提供完整的基因副本，你只能插入那些与病毒中的其他调控元件完全匹配的基因。所以，在所有编码蛋白质的基因中，由于我们通常针对影响蛋白质的疾病进行治疗，其中80%的基因可以适应我的病毒。因此，实际上绝大多数遗传性疾病可以通过AAV基因治疗进行治疗，通过基因转移基因治疗进行治疗。
With gene editing gene therapy, we can treat anything because now we're not size limited. We only need to deliver either the nicker or the cutter, right? Many of you have heard of things like CRISPR. That's one of the many tools we can use to nick or cut DNA. And we can either make a nick and have your body repair the mutation. We can go in and make a nick or a cut, and we can cut something out that wasn't supposed to be there. Or we can go in and nick or cut something in your genome, cut something out, and then put something that was meant to be there the whole time back in. All three of those forms, those gene repairs and gene edits are all kind of broadly classified as gene editing gene therapy. And all of those would fit within any virus.
通过基因编辑基因疗法，我们可以治疗任何疾病，因为现在我们的治疗不再受限于大小。我们只需要输送切器或剪刀，对吧？你们很多人可能听说过CRISPR之类的东西，这是我们可以用来修剪或切割DNA的众多工具之一。我们可以做一个切割，然后让你的身体修复突变。或者我们可以进入体内进行切割，切除本不应存在的东西。或者我们还可以进去修剪或切割你的基因组，切掉一些东西，然后重新放回本应一直存在的东西。这三种形式的基因修复和基因编辑都被广泛归类为基因编辑基因疗法。而所有这些都可以适用于任何病毒。
There's a high percentage of disease, I don't know the percentage you probably know, which is really just like one point mutation, right? Yeah. Huge transcribe AC or something is typically the biggest one, right? Can you just explain to folks, when you think the tool chain will exist for us to do those single point edits and actually just. Today. You can actually go in and accurately rewrite an A to a C. Today. Yeah, there's a few in. Yeah, there's some.
目前有很高的疾病发生率，具体比例我不太清楚，你可能知道，这很像只是一个点突变，对吧？是的。巨大的转录AC或其他东西通常是最主要的原因，对吧？你能解释一下，当你认为我们将有能力进行这些单点编辑并且真正实现的工具链将会出现吗？今天。今天，你实际上可以准确地将A改写为C。是的，有一些。
.ckerels and almost approved. Yeah.
.ckerels几乎获得批准。是的。
So, um, guys, we gotta wrap and I want to really thank Dr. Nicole Paulk for her amazing work and for joining us. Thank you. Thank you. Okay. Fantastic.
嗯，各位，我们必须结束了，我想非常感谢尼科尔·保尔博士的出色工作和加入我们的时间。谢谢您。谢谢。好的，太棒了。
Thank you so much. Thank you. Thank you. You got a nice standing here. Thank you. Thank you.
非常感谢你。谢谢你。谢谢你。你在这里的位置很好。谢谢你。谢谢你。
You've got a nice standing here. What are you doing? I'm doing your winter slide. Rain man, David Saffs. I'm doing it all. And it said we open sources. And they've just gone crazy with rain. Romulus. Nice. We know we know we're gonna survive.
你在这里的地位不错。你在做什么？我正在为你做冬季滑道。雨人，大卫·扎夫斯。我全都在做。而且它说我们开源了。他们刚刚为雨疯狂了起来。罗穆卢斯。不错。我们知道我们会活下来的。
What? What? What? What? What? What? What? What? What? What? What? What? What? What? What? What?
什么？什么？什么？什么？什么？什么？什么？什么？什么？什么？什么？什么？什么？什么？什么？
这句话重复了"什么"这个词十五次，用来表达疑惑、困惑以及迷茫的情绪。