A Revolutionary Biocontrol (and Delivery System)

On Christmas Eve 2020, a group of scientists released a report on a revolutionary new method for battling COVID-19. As a couple of ag researchers read through the findings, they became more and more excited. The potential of the described technology seemed almost limitless.  

Nanobodies, a tiny piece of the antibody cells found in the camelid animal family (camels, llamas, and so on), could interfere with just about any cellular organism, including bacteria and viruses.  

One of those scientists reading the study results was Michelle Heck, Ph.D., Lead Scientist and Research Molecular Biologist, USDAARS, who quickly reached out to her Florida colleagues, Robert Shatters, Ph.D., Director, European Biological Control Laboratory, USDA-ARS, and Marco Pitino, Lead Project Scientist at AgroSource. They were leading a team trying to find a way to battle citrus greening, an invasive disease with no known cure. The bacterial disease, vectored by the citrus psyllid, is slowly destroying the Florida citrus industry.  

All three lead scientists will discuss their work at the 2023 BioSolutions Conference & Expo in Reno, NV, on February 23.

A technology that holds promise to finally fight back citrus greening is revolutionary enough. A technology that can potentially treat any disease in any organism is a game changer.  

Naturally, we had a lot of questions on nanobodies. Here is a small part of the conversation we had with Heck and Shatters.  [To see the full version of this interview, check out the original article in our Global Insight Series: Plant Health report.

Q: What, exactly, are nanobodies? 

Heck: All organisms have an immune response, an immune system. When most animals produce antibodies, the antibodies are gigantic. Camelids produce an antibody that has a very small domain with the function to recognize the antigen independently from the rest of the antibody molecule. And this is what’s called the nanobody.  

Nanobodies are so small and structurally diverse. They can do things in terms of protein interactions that larger antibodies can’t successfully do. One of them is to move systemically throughout the plant’s vascular system, enter cells, and bind to regions of proteins that larger antibodies can’t have access to.  

Q: How do nanobodies work? 

Heck: [In citrus greening], the bacteria express these little weapons proteins called effector molecules/ effector proteins. If the bacterial infection starts here in the plant or on this leaf, the bacteria will secrete effector proteins that move to the other part of the plant to dampen the plant’s immune system and create an environment that supports pathogen growth.   

And so, we hypothesized that if we developed a way to block those bacterial effector molecules from working, we could stop the infection process in its track. 

Shatters: So, if you block those proteins from their function, symptoms don’t develop, the bacteria can’t replicate, and so you’ve stopped the disease cycle.  

Q: A big part of your work was on how to deliver the nanobodies to the plant. You needed something you that could make it to market relatively quickly and that was likely to make it through regulations.

Shatters: They’re biological molecules. They’re expensive. You can’t spray and get, say, less than 1% taken up in the tree. It’s just not feasible.   

So, we stepped back. [We considered] how long it will take to register, if will it be accepted, and so on.   

Join us at BioSolutions Conference & Expo, where these three lead scientists will update us on their next steps on this game-changing work.

One of the things that came up over and over was this idea of, what if we could make something like an insulin pump they strap on a tree and it delivers a proper dose over time? But we’ve got to do it biologically, because we can’t afford to put a mechanical pump on every tree.   

But if the tree could do that …   

And so we came up with this concept of [a plant symbiont]. We take some cells from the plant, modify them with genes to produce growth hormones, so they grow into what we call a symbiont. It’s a group of citrus cells that grow where they are attached to the tree and do not move from that location.   

X