Revolutionizing Antibody Production: Leveraging mRNA Technology in Cell Culture Systems

Introduction

This idea arose from my curiosity – why mRNA was used to get the body to make antibodies, instead of just making the antibodies in a lab and injecting them. Both are actually used, but the latter is apparently more expensive. I couldn’t see why, given the existence of lab-cultured meat these days and its rapid progress. In my experience, quite simple things often get overlooked because they are in different industries, and many novel ideas happen simply by taking an idea from one industry and applying it to another. I’m not an professional biologist, but enjoy paddling in the easier fringes of the biotech field. This idea might be of use, in which case, feel free to use it, and buy me a crate of beer when you make your first million. ChatGPT thinks it’s good, but it uses a very low bar.

The production of monoclonal antibodies (mAbs) plays a crucial role in modern medicine, offering targeted therapies for a wide range of diseases, including various cancers, autoimmune disorders, and infectious diseases. Traditionally, these antibodies are produced using recombinant DNA technology in mammalian cell lines, a process that, while effective, involves complex genetic engineering and lengthy cell culture operations. The emergence of mRNA technology, highlighted by its pivotal role in rapid COVID-19 vaccine development, presents an innovative opportunity to revolutionize antibody production. This proposal explores the potential of employing mRNA technology to instruct cultured cells to produce specific antibodies, offering a novel, efficient approach to biomanufacturing.

Concept Overview

The core of this innovative approach involves synthesizing mRNA sequences that encode for desired monoclonal antibodies and introducing these sequences into suitable cell cultures. The cells, upon taking up the mRNA, translate its sequence into the target antibody proteins, essentially turning the cultured cells into efficient, scalable antibody factories. This method combines the specificity and versatility of antibody therapies with the rapid production capabilities of mRNA technology.

Technical Rationale

1. mRNA Synthesis and Design: Custom mRNA sequences corresponding to specific antibody proteins are designed and synthesized, incorporating necessary regulatory elements to optimize translation efficiency and protein stability within the host cells.
2. Efficient Transfection Methods: Advanced transfection techniques, such as lipid nanoparticles (LNPs), electroporation, or non-viral vectors, are utilized to deliver the mRNA into cultured mammalian cells, ensuring high uptake and expression rates.
3. Cell Culture Optimization: Cell lines traditionally used in antibody production, like Chinese hamster ovary (CHO) or human embryonic kidney (HEK) cells, are optimized for growth and antibody expression in response to the introduced mRNA, leveraging existing bioreactor infrastructure for scalability.

Advantages

• Speed and Flexibility: The ability to rapidly synthesize and modify mRNA sequences allows for quick adaptation to produce different antibodies, making this approach highly versatile and responsive to emerging medical needs.
• Simplified Genetic Engineering: By bypassing the need for complex genetic engineering of host cells, this method simplifies the production process, potentially reducing development times and costs.
• High Scalability: Utilizing cell culture systems and bioreactors already in place for biopharmaceutical manufacturing, this approach can be scaled efficiently to meet high-demand scenarios.

Challenges and Future Directions

• Transfection Efficiency and Stability: Optimizing the delivery of mRNA into cultured cells and ensuring its stability for sustained protein production are critical technical challenges that require innovative solutions.
• Regulatory and Quality Control: As with any novel biomanufacturing process, establishing rigorous quality control measures and navigating regulatory approvals are essential steps toward clinical application.
• Cost-Effectiveness: Evaluating the economic viability of this method compared to traditional antibody production techniques will be crucial, considering factors such as mRNA synthesis costs and the efficiency of protein yield.

Conclusion

The proposal to utilize mRNA technology for the in vitro production of antibodies represents a significant leap forward in biomanufacturing, combining the precision of antibody therapies with the rapid, flexible production capabilities of mRNA. By addressing the technical and regulatory challenges, this approach has the potential to streamline antibody production, enhancing the ability to respond to global health challenges with unprecedented speed and efficiency. This innovative intersection of biotechnology and mRNA science heralds a new era in therapeutic development, promising to impact profoundly the landscape of medical treatment.

Antibody test results could be bad news

Another ‘I’m not an epidemiologist but’ article. As usual on this theme, please don’t read too much into it, it may well be nonsense.

Progress on producing antibody tests have shown that many under-40s don’t produce many antibodies. It is possible that instead, their T-cells simply destroy the virus without requiring antibodies. 

https://www.telegraph.co.uk/news/2020/04/15/uk-coronavirus-antibody-test-validated-results-show-under-40s/

That might at first look like good news – young people don’t even need the antibodies, they have such wonderful immune systems that they just deal with the viruses directly – but it isn’t.

As the article points out, this may firstly hinder the possibility of producing virus immunity certificates, because it would be difficult to prove that a young person has had the disease, and secondly, may indicate likelihood that that person may become infected again. If that is true, herd immunity might be impossible to achieve.

Immunity certificates are problematic in any case, making two tribes with conflicting interests:

When two tribes go to war

The second effect is much more worrying, and even more so if you believe (as I do) that the virus resulted from meddling with one from bats to produce versions that can better attack humans.

Viruses use proteins to fuse with target cells. The gp41 protein used in the coronavirus is the same as that used in both HIV and its sister virus HTLV-1. Both of those target T-cells, a major part of the body’s immune system, and remain permanently in the body for life. By infiltrating and sabotaging the immune system in this way, they cause repeated and sometimes serious illnesses by disrupting the immune system.

If we were to indulge in pure speculation, a military looking to produce a virus that could bypass the human body’s immunity might well consider using such a proven mechanism. It would be somewhat consistent with early candidate shortlisting for future bioweapon research. At such early research stages, military intent could easily be hidden. Investigating classes of viruses and their impacts on humans could be entirely benign, looking for potential new medicines for example. At early stage investigation, it is perfectly possible that it might take place in a medical research establishment, staff might well not be fully aware of the purpose of their research, and full precautions might not be taken, hence the unfortunate researcher infection, release and the resulting pandemic. The accidental release at such an early stage could explain why the disease only has weak lethality and infection compared to high infection, high lethality you might expects from a military virus.

Without the speculation, the virus does nevertheless exist, does have its particular properties, and is causing its problems, regardless of its origin. It does not have to have been deliberately created to be harmful.

If the virus does work similarly to HIV/HTLV-1 in young people, that is bad news. They may initially escape the worst effects of the virus immune response, not becoming seriously ill immediately, but that doesn’t mean they are safe. If the virus stays in their bodies for life, there will be plenty more opportunities for it to flare up. Worse, by effectively sabotaging the immune system, HIV and HTLV-1 can cause other diseases such as cancer, neural degradation, loss of consciousness, severe pain, angina and many other problems.

The lack of antibodies could therefore be an early indication that the virus is not so much destroyed by the young people’s T-cells as merging with them and infiltrating the immune system in a similar way to HIV or HTLV-1, that both use the same gp41 fusing protein. The bad effects we see now on older people showing severe immune reactions might be followed down the line by large numbers of younger people exhibiting AIDS-like problems.

It might also be bad news for development of a vaccine. I suspect that a vaccine for COVID-19 might use similar principles to one for HIV or HTLV-1. However, we’ve spent 40 years looking for an HIV vaccine, and have barely even started looking for one for HTLV-1. There have been some successes on HIV vaccines, but most have been disappointing: http://www.aidsmap.com/news/mar-2020/hiv-vaccine-generates-broadly-neutralising-antibodies-passes-first-safety-and-proof.

A vaccine against SARS-CoV-2, the virus that causes COVID-19 might well face the same problems, but progress in HIV viruses might speed up search for COVID vaccines. However, looking at the results of the antibody tests, it could well be that a vaccine only works for some people.

It’s too early to say. All of this might be nonsense. But I think it’s also too early to say that until we know more about why young people are not generating antibodies. It might be that the problem will stay with us far longer than we had hoped, and that we’re only seeing the first stage of its effects.