Industry Insights with Yuning Chen on Recombinant Proteins This episode of Share Science features Yuning Chen, PhD , an R&D manager at Sino Biological . Sino Biological has an extensive library of recombinant virus proteins known as the ProVir collection, and in this interview, Yuning shares the importance and value of these high quality reagents. LISTEN TO THE PODCAST:

What are recombinant virus proteins and how are they made?

Viruses are composed mainly of protein and genetic material, which is either DNA or RNA. Proteins are important for viral functions like replicating, interacting with the host, and achieving correct assemblies. In general, directly working with highly potent viruses is dangerous. One way to get around this issue is using the recombinant format of these protein components in various studies.

I think the importance of these recombinant virus proteins is that they can serve as a surrogate for the real virus so we can interrogate different aspects of a certain virus [and] better understand [its] biology, physiology, and functions.

Recombinant virus proteins are made by a technique called recombinant expression, which has been around for almost five decades now, I think. It's a relatively old technique, but it's improving all the time. In this process, we take the gene fragment that encodes the protein of interest (in this case, a protein from a virus) and put it into a vector, normally in the format of a plasmid. Plasmids are circular DNAs you can find in nature, mainly in some bacteria. We take this plasmid that contains the gene of interest and put it into a host cell. Basically, we use cells to help us mass manufacture these proteins. The host cells can be prokaryotes like Escherichia coli , which is one of the main workhorses in this industry. We also have eukaryotic systems such as yeast, just like what you use to make bread, as well as insect cells and even mammalian cells.

We have all kinds of host cells, and depending on the characteristics of the virus protein, we pick one that will give us maybe the best results.

We insert the plasmid containing the proteome (i.e., the gene of the protein of interest) into the host cell which has a protein manufacturing machinery that essentially mass produces this virus protein. At the end of the culturing cycle, we can harvest the cells or the culture supernatants and purify the virus protein with either the cell lysate or culture supernatant. This way, we can have an infinite supply of virus proteins to conduct all kinds of research.

Why do we need recombinant virus proteins and how are they used in infectious disease research?

Like I mentioned earlier, directly working with viruses can be dangerous sometimes, especially those categorized as biosafety level four pathogens such as Ebola or Marburg virus. Since viruses mainly use proteins to carry out their various biological functions, proteins are very important tools for us to understand certain aspects of a virus. We can obtain recombinant virus proteins in relatively large quantities. Since theyre not a whole virus, they're not infectious, giving researchers a lot of freedom to investigate biophysical properties. For instance, people have heard a lot about SARS-CoV-2 spike proteins, which is the protein that interacts with host cells. Instead of working with a live virus, researchers can safely work with the spike protein.

We can also make the spike protein of [different SARS-CoV-2] variants and establish how they interact with host cells.

With different versions of this spike protein from different variants, scientists can assess how these proteins bind to receptors like ACE2 and its binding strength. Essentially, these recombinant virus proteins can give us tools to understand the physiology and biology of the virus without actually working with the virus. Although recombinant virus proteins are only part of the virus, some of the key physiological traits of the virus can still be sufficiently determined.

How are recombinant virus proteins used to develop vaccines and antiviral therapeutics?

This is a big topic: recombinant virus proteins can be used directly as vaccines. Vaccines come in different shapes and formats; some of them use inactivated or deactivated viruses, some of them use messenger RNA (mRNA), and some are protein subunit vaccines which are derived from recombinant virus proteins. I think there are several companies in China that are developing second generation recombinant subunit vaccines based on the SARS-CoV-2 spike protein.

Recombinant virus proteins can indeed be used directly as vaccines or as tools to help vaccine development.

In terms of antiviral therapeutics, viruses have different parts. Let's use SAR-CoV-2 as an e