The Power of Transient Protein Expression in Vaccine Development

Podcast: Discover how Expi protein expression systems offer speed and flexibility to move candidates into clinical trials with the highest chance of success

Transcript

Interviewer: BioPharm International

Interviewee: Dr. Henry Chiou, Director of Protein and Viral Expression Systems and Transfection at Thermo Fisher Scientific

BioPharm:
How are Thermo Fisher Scientific’s protein expression products aiding biotech and pharmaceutical companies with efforts to combat coronavirus?

Chiou:
COVID-19 is a major global issue that we all want to resolve as quickly and as effectively as possible. Thermo Fisher Scientific’s Gibco Expi293 and Gibco ExpiCHO Expression Systems have been specifically designed to provide tremendous speed and flexibility for protein expression, both in terms of time and the quantity of protein or protein complexes that they can produce.

For those who may be less familiar with it, Thermo Fisher Scientific defines its transient expression systems as those that can directly transfect, in bulk, suspension-adapted cells, typically either human embryonic kidney 293 cells (HEK293) or Chinese hamster ovary (CHO) cells. We transfect them with a gene (or genes) of interest and then harvest for the expressed recombinant protein from this transiently expressing cell, usually within 4–10 days post-transfection. In most cases, we can generate milligrams to grams of protein in bench scale, shake flasks, or small bioreactors. Our Expi systems are designed with high-yield cells adapted to high-density cultures with three- to six-fold more cells per milliliter than classic transient expression systems.

This combination of high-yield cells with the much higher number of cells per milliliter increases protein yields many-fold for most proteins that labs have tested in these Expi systems, and specifically, for COVID-19, the SARS-CoV-2 viral spike protein. Many labs have been using our Expi293 system and report very good yields—as much as 10-fold higher than most other transient systems—with expression times of only 3–4 days.

In parallel, there are several biotech labs that are successfully using our ExpiCHO System to develop and express vaccine candidates against the virus. The speed of these transient expression systems and the high yield are imperative to express and screen many different candidates and variants and move towards clinical trials with the highest chance of success. This applies not only to vaccine development, but also the development of diagnostic assays to detect or monitor COVID infections as well as the identification, development, and potential therapeutic modalities against COVID-19.

BioPharm:
Is there a lot of versatility with protein expression systems, and how this will benefit biotech customers?

Chiou:
Proteins are critical to human health and act as primary players in the occurrence and lifespan of disease. They are a wide and diverse class of molecules, so we need to have protein expression systems that can express a variety of proteins for disease modeling, target identification, drug development, the development of biologics, and so on.

The most common use of our transient expression systems is for the production of monoclonal antibodies (mAbs) and the derivatives of them. mAbs tend to express pretty well, and many labs have been able to generate yields of hundreds of milligrams to grams of antibody per liter of transfected culture. The ExpiCHO cells are particularly good at generating high yields of antibodies and derivatives and often are averaging about twice as much yield as an Expi293 system for antibodies. Membrane proteins are another important category of proteins. This is a valuable druggable protein class.

There are an increasing number of labs reporting the use of our Expi systems, particularly Expi293 for expressing G protein-coupled receptors (GPCRs), and many labs report some of the highest yields from a mammalian system from our Expi293 System. In some instances, the GPCRs that are expressed have much higher thermal stability than the same protein when they try to express it in Escherichia coli and at higher overall yields compared to bacterial systems. Thus, there are many different types of proteins and protein assemblies that can be produced using these transient expression systems, and this gives biologic scientists a lot of versatility and utility for biotech labs.

BioPharm:
Where do you see the future of protein expression, and what untapped capabilities does Thermo Fisher Scientific have to offer?

Chiou:
We are continually working on further development and refinement of our transient expression systems so that we can meet the ongoing needs and applications for the biotech and pharma industry. One area that the COVID-19 pandemic has highlighted is that labs want to go fast in terms of vaccine diagnostic and therapeutic development, in both early discovery and preclinical stages. Labs also want to accelerate these candidate molecules into clinical trials and commercial production so that these needed solutions can get to patients and the general population as quickly as possible.

One thing you will see as we continue to evolve our transient expression systems are fully regulatory compliant GMP documents that can be used to produce products not only for research, but also for clinical trials and even for a potential manufacturer of approved product. In this way, we can truly provide a streamlined and consistent workflow from the research bench all the way into the administration into humans. Obviously, we have a lot of capabilities within Thermo Fisher Scientific to support regulated production and clinical work. That is what we hope to leverage as we continue to evolve our systems.