From Protein Science R&D to Therapeutics: Expert Insights (Part 1)

Ann Nguyen:
Hello. This is Ann Nguyen, Senior Associate Conference Producer with Cambridge Healthtech Institute. We are here for a special two-part podcast series for PepTalk: The Protein Science Week, which runs January 9-13 in San Diego, California.

Today, we're featuring insights from protein science experts who are part of the "It's a Wrap" Closing Plenary Panel Discussion, which represents various R & D stages that are, in turn, encompassed by the seven topic pipelines at PepTalk.

We've asked today's experts the same question: What do you see as the next, most promising innovation in your field? Here's Dr. Thomas Laue, Professor of Biochemistry and Molecular Biology and Director of the Biomolecular Interaction Technology Center at the University of New Hampshire. He represents the Formulation & Stability pipeline.

Thomas Laue:
I believe that the most important thing is to come up with better predictive means of determining the solubility and viscosity of protein solution to high concentrations. At the moment, these techniques are not very successful. What we need to do is be able to go from either structure or initial measurements of some sort to being able to determine whether there's going to be difficulty manufacturing a protein or difficulty with viscosity dispensing the protein.

There's work going on in this area. Right now, we're still at the stage where we're gathering the data necessary to learn how to make these predictions. In particular, we need to have more data on viscosity of protein solutions as it relates to other physical properties, in particular to the charge on the protein or possible on the dipole moment of the protein. There are instruments available for making these two measurements and they would be very helpful in terms of being able to cut the costs and cut the time from the point of determining a candidate molecule to the time that that molecule is actually put out for use.

Ann Nguyen:
Here's Bjørn Voldborg, Director of CHO Cell Line Development with the Novo Nordisk Foundation Center for Biosustainability at the Technical University of Denmark, representing the Biotherapeutic Expression & Production pipeline.

Bjørn Voldborg:
I think that the continuous development of the CRISPR-based tools that we have might be the most, biggest innovation possibilities, not only to engineer the cells by knocking out genes, but actually also being able to target a lot of transcription factors and silencers and others to the specific areas on the genomes, thereby actually being able to manipulate the cells’ behavior in a very refined way. I can see that as a possibility in the future, which will make it possible to induce possibly even different responses during the production of the proteins, so during the different phases can actually turn on or turn off genes that might or might not be beneficial for the production.

Ann Nguyen:
Here's Dr. Andrew Fosberry, Senior Scientific Investigator in Protein and Cellular Sciences at GlaxoSmithKline, representing Process Technologies & Purification.

Andrew Fosberry:

Where I think things are going for the future that will enhance discovery in my field is the area of what I call designer microbes. This is using the current enhanced toolbox that we have from a synthetic biology point of view, and that includes how we can seek those genomes using the next-generation sequencing technology that's out there now. How we can use the new molecular biology techniques such as Gibson Assembly, CRISPR/Cas9, etc. These are all new technologies that are actually coming to the fore on a monthly/yearly basis. Basically, technology is changing at a huge pace and these are actually giving us a huge choice of tools that will enable us to actually build the microbes of the future.

What I mean by designer microbes is, if we go back a while when I first started working in the industry, we had microbes that produce certain secondary metabolites. We didn't know how they produced them, what pathways were involved, etc., etc. If we wanted to enhance them, we would take the masses of random mutagenesis, screen thousands upon thousands of different mutants to come up with one that maybe produced slightly more than we actually had to start with.

We didn't know why it produced slightly more than when we started, but with the tools of today, what we can do is with next-generation sequencing, we can actually sequence a genome overnight. We can be looking and annotating the data the next day. We can zero in on pathways or genes involved in what we think is the metabolon that we're interested in and change those for the better. We can knock out pathways. We can knock in pathways using CRISPR/Cas9. We can move pathways from one organism or microbe to another, which may be beneficial, and that's what we would hope. If the actual microbe had some of the benefits that we wanted, we can also use the new evolution technologies that are out there with higher screening capabilities. We can actually explore the whole diversity of our evolution libraries to actually zero in on the mutants or the enzymes that we really want.

Ann Nguyen:
That wraps up Part 1 of this Q&A series. Stay tuned later for Part 2 with more expert panelists.
All of them will be discussing the future of protein therapeutics, challenges and highlights from PepTalk: The Protein Science Week's presentations at the Closing Plenary Panel "It's a Wrap". The panel takes place the last day of this event, which runs January 9-13 in San Diego, California.