Genetic Medicine: Overcoming the Challenge of mRNA Delivery for Targeted Treatment

One of the “four pillars” of innovation and technology development in Hong Kong is Life Science, which I am relatively unfamiliar with. From the Hong Kong founders I have contacted in the past, I found that most of them are either university professors or their favorite students. Unexpectedly, I found a “Zhongtong” in London who I hadn’t seen for many years. Albert Kwok, a young British scientist and founder. The company focuses on genetic medicine and was selected into Y Combinator in 2021. Cowork chatted for a while, the content is very exciting, this time I intend to prepare a Q&A draft, and use his experience and sharing to introduce genetic medicine to readers in Hong Kong.

It is understood that Nuntius Therapeutics entered YC in 2021. What is the current topic and what products are they making?

（A = Albert ｜M = Mickey）

A: When we make gene therapy drugs, we will use DNA or the mRNA we are very familiar with. Taking COVID vaccine as an example, mRNA can actually be very useful. Similarly, we can use mRNA to make medicine, which can also be very powerful. Instead, the biggest challenge now is how to bring medicinal mRNA into the desired cells. . For example, if you have a lung disease, if you want to use an mRNA drug, you have to bring this drug to the cells in your lungs to have medicinal value. So the biggest challenge now is to There is a delivery method and system to deliver mRNA to the cells you want to go to. What our company is doing is the mechanism of delivering mRNA, and we are temporarily focusing on anticancer drugs.

M: The principle is the same as the COVID vaccine?

A: In terms of COVID, we mainly want to bring mRNA into a kind of immune cell after injection, and that immune cell will make mRNA into a protein (protein), and this protein will tell some specific immune cells, such as T cells (T lymphocyte), teach them that next time they see a similar protein, you have to annihilate it. In fact, the so-called “similar protein” is one of the components of the COVID virus. Sometimes, when the virus mutates, the shape of some of its own proteins is also different. At that time, we need to use a different mRNA sequence to make this new protein.

Which diseases can be overcome and treated by mRNA? Which diseases are more difficult? Can you give some examples?

A: For the time being, medicines such as mRNA can be used to treat most of the diseases known to humans to be related to genetics. For example, there may be some problems with your genetics that prevent you from producing some normal proteins. It may be possible to adjust it so that it can produce normal protein to have a curative effect, similar to COVID-19, it can be used as a vaccine type of medicine. There are also some diseases that are more difficult to challenge. For example, some diseases are related to the environment in which the patient lives, and the genetic basis of some diseases may not be so clear, so it is more difficult to use mRNA for drug treatment.

M: In recent years, it seems that many cancers may be treated with mRNA, right?

A: It is because we are now doing cancer research and found that many times in many cancer cells, they will produce some very strange proteins, those proteins will not be found in your normal cells, so now a lot of research, let’s start to look at some of them New proteins will be produced by cancer cells but normal cells will not. When you can, you can bring your immune cells to your immune cells by planning the same protein produced by mRNA, and then those immune cells educate T cells or B cell, the next time it sees this protein, it will deal with related cancer cells, in this way as a new anti-cancer method.

M: So you just talked about this case, is it a preventive measure, or a means of treatment after diagnosis?

A: At this time, it is more a medical method. Imagine a cancer patient. The steps are that you first obtain T-cells from his cancer cells, and do some DNA sequencing to see if it will produce new lesions. When you find the protein of these lesions, you can start the above treatment.

Speaking of so-called “DNA sequencing” technology, this approach to medicine feels personal?

A: Yes, it is definitely a personalized medical approach. The two COVID vaccine companies we are familiar with, including Moderna and BioNTech, have actually started some clinical trials in cancer treatment.

M: The cost of personalized medicine must be very high? Have they all gone through clinical trials, or are they still in the research and development stage?

A: Both of the above two companies are already in clinical trials. They are both in the early stage of clinical trials, but they already have data. They seem to be very promising. They will do more clinical trials in the future.

M: Is it possible to develop a preventive vaccine against cancer?

A: In terms of medical treatment of vaccines, I don’t think there will be any for the time being. No company is currently researching, but I believe there will be another big revolution. Many DNA sequencing and RNA sequencing will be used in the field of cancer, such as these Technology to understand patients’ genetic makeup, and many companies are now doing this type of research.

It sounds like DNA sequencing is the key technology, can you introduce the principle?

A: Simply put, DNA sequencing is to look at the whole DNA sequence in your cells. If you know these data, you can know the relationship between some diseases and some DNA mutations. Similarly, you can know how likely you are to develop those diseases, and you can make a prediction.

M: The matter of DNA was first proposed in 1953. It was a long time ago. Why did it take so long to develop into today’s DNA sequencing?

A: At that time, it was 53 years. It should be the discovery of DNA structure and their identification DNA basic component. At that time, the knowledge was to know how it controls the function of cells, and then to know that DNA has 4 chemical components, but there was no way to know those components at that time. At that time, there was actually no in-depth understanding of how to connect and what different connections would do.

Afterwards, the breakthrough of DNA sequencing came from a scientist named Frederick Sanger, who probably developed the technology of DNA sequencing in the 1960s and 1970s, and later generations called it Sanger sequencing, which made gene therapy theoretically feasible. But to count the breakthrough of real DNA sequencing, I think it should go to the 1990s.

If you have the impression, the Human Genome Project of the U.S. government was designed to map the human genome and identify the genes and sequences contained in it, so as to achieve the ultimate goal of deciphering human genetic information. At that time, it took about 10 years to sequence the DNA Sequence of several people, possibly using billions of dollars of funds, and it was even more impossible to use the technology at that time to do personalized sequencing. Around 2005 to 2006, the so-called “Next generation sequencing” began to appear, which could quickly sequence many DNA fragments and then use them to build the entire genome.

Is there any relationship between the rapid development of AI in recent years and the recent outbreak of Generative AI?

A: In terms of studying DNA, it is related to the development of AI, because next generation DNA sequencing and other related new technologies around this sequencing make it possible for us to sequence the entire human genome, such as your and my DNA, Now in fact, find some laboratories and do it in a few weeks. In short, it is no longer a few decades.

In other words, many different units can sequence the patient’s genome, and then find out whether there are some mutations that make it diseased. This is the research direction of the past 10 years. Since DNA sequence can extract a lot of data, which may be closely related to the symptoms of patients, in this respect, machine learning or AI can have a perspective to discover some hidden links.

M: There are also some biomed startups in Hong Kong, which aim to find the link between some existing drugs and specific genetic diseases.

A: Yes, because in the past few years, a lot of research has begun to appear, and it is found that there may be some mutations in DNA that will cause you to produce some strange proteins, and you may find some existing drugs that can be added on to remove these so-called “weird proteins”. Before that, you may not have known before that this disease has this problem. It doesn’t have to be a brand new drug, it might have existed before, but you didn’t know that it could be used exactly in this way, and now paired, it can cure such a disease.

From the perspective of investors or market reaction, which sector of Genetic Medicine is more popular?

A: In terms of the investment market, I think the most funds will be invested in treatment, because the scope of treatment is very broad. The first is that you may follow what you said just now. It may be because you will find that there are already some drugs on the market. In fact, there may be an add-on problem. The second is that there may be no such drugs on the market. You can use mRNA or DNA technology, yes It is easy to print the mRNA out.

The so-called “Print” means artificially manufactured, such as COVID mRNA vaccine. When the print comes out, the mRNA has a standardized method, and a specific sequence can be produced. After it is produced, it is not necessarily a virus that enters the body, but some artificially produced proteins can also be used.

M: What is the research direction of your company?

A: In fact, after I print it, I put it in the medicine. At present, the main mRNA medicine is injection. There is a lot of effort in technology now, in fact, it is to find ways to protect mRNA. How to have a feasible vehicle to deliver to the cells you want is the key to technology.

M: Returning to the cancer genetic medicine market, how far is it from the popularization of the product?

A: I think everyone can take a more optimistic attitude, because I believe that in the next 5 to 10 years, many cancers should be cured, which is really a good thing.

Interview: Yin Sizhe