Similar innovations have occurred in agricultural research—though much more slowly. Over the past 10 years, a niche group of plant scientists have been working toward a similar goal: delivering RNA into cells to temporarily shift their activity. Although the impacts on human health are not as obvious, these technologies could improve nutrition, protect the environment and reduce the cost of food.
But without a threat such as a global pandemic, will RNA-based plant applications ever reach the field? Funding for plant research is hard to come by and biotech innovations in agriculture face significant regulatory hurdles. Yet a recent study from Kyoto University has made progress toward field-ready RNA-based technologies. Space scientists hope that, like vaccines, this approach will follow an accelerated path to approval.
COVID-19 RNA vaccines are essentially RNA packaged into lipid (fat) nanoparticles. When RNA is delivered into cells, it is transcribed into a piece of viral protein that our immune system can recognize. This recognition mounts a response that protects us from future infections.
RNA tells cells which proteins to make. RNA can also tell cells to stop making certain proteins in a process known as RNA interference (RNAi).
Although plants do not have adaptive immune systems like animals, they can still recognize, “remember”, and react to threats. In 2019, researchers from the Institute of Biochemistry and Biotechnology in Germany demonstrated that RNA introduced into plants protects these plants from viruses via RNAi.
In a related approach, a USDA-led group of scientists found that RNA delivered into the plant vascular system (veins) can fight off the pest that spreads citrus green leaf disease. Citrus greening has been in the news lately due to rising orange juice prices. Florida is expected to produce 1.5 million fewer cases of oranges this year as groves are decimated by disease.
While most studies introducing RNA into plants have focused on defense against insects, bacteria, fungi, or viruses, the same approach could apply to all sorts of traits. For example, drought tolerance is tricky because drought-resistant plants produce less than drought-sensitive plants when it rains. Imagine using RNA to stimulate drought response genes only when dry.
Many traits that crop scientists have experienced through genetic engineering could instead be controlled by RNA/RNAi. This includes genes important for food spoilage, herbicide resistance, medicinal/nutritional compounds, and pest/disease resistance. But first, there are a few technical challenges to overcome.
The challenge of RNA delivery
Part of what’s so amazing about RNA-based COVID-19 vaccines is that they work at all. RNA is incredibly unstable. There are a host of enzymes called RNases waiting to chew on RNA.
One of the most important innovations of RNA vaccines is their delivery system. Lipid nanoparticles, which were developed primarily for anti-cancer drug delivery, have been adapted for RNA.
Injecting individual humans with RNA-containing lipid nanoparticles is logistically challenging, but not impossible, even on a global population scale. Injecting RNA into individual plants would be ridiculous, even on the scale of a personal garden, let alone the global food supply.
Hence the main technical challenge of using RNA in agriculture: how to deliver RNA into plant cells on a practical and cost-effective scale?
It turns out that the solution is quite elegant. In a study published this month, researchers at Kyoto University have developed a topical spray containing RNA that alters gene activity in tomatoes by more than 80%.
Instead of lipid nanoparticles, they used vessels composed of peptides or small proteins. This is important because the spray must include a surfactant, such as soap, to break through the waxy surface of the plant leaves. The surfactants would probably destroy the lipid nanoparticles.
This was not the first time a spray application had been used to deliver RNA into plant cells. What was important in this work is that they also activated RNAi in chloroplasts.
Chloroplasts contain their own small genome. And the chloroplast houses the major isoprenoid production pathways. There are approximately 50,000 different plant isoprenoids and their importance ranges from medicinal (THC and Taxol) to industrial (rubber and dyes) to sensual (flavor and fragrances). The manipulation of isoprenoids and other important metabolic processes via RNAi must occur in the chloroplast.
Moreover, it was previously unclear whether or not RNAi occurred even in plastids. A very recent study detected RNAi in human mitochondria (also an organelle containing the genome), but the jury was still out on plants.
The potential for RNA-based plant manipulation is clear. And great strides have been made in overcoming technical challenges over the past 10 years. But when these innovations are ready in the field, how will they be regulated?
Regulation of RNA applications
Assuming you received the COVID-19 vaccine, I doubt you would consider yourself a genetically modified human. Similarly, the current regulatory structure would not consider a plant sprayed with RNA as a genetically modified organism (GMO).
The regulations regarding what is and what is not a GMO are oddly specific. For example, a plant variety that was created by treating its ancestors with radiation or mutation-inducing chemicals is not considered genetically modified, even if it contains many known and unknown mutations. Conversely, if a gene from one variety of tomato is inserted into another, that tomato is considered a GMO, even though the genetic modification may have occurred naturally through selection.
Remember the scientists fighting citrus greening with RNAi? There are already genetically engineered orange trees that are resistant to citrus greening, but approval could take another 10 years, and citrus greening has been wreaking havoc for almost as long.
The researchers behind citrus greening and other RNAi projects hope that this technology, once perfected, can be used quickly to adapt to growing threats at a pace similar to the COVID-19 response. . If they’re right, RNAi may be just the start. There is reason to believe that CRISPR-based systems could be delivered in the same way, opening the door to a host of temporary/targeted genetic alterations.
Jenna Gallegos is a freelance writer and holds a PhD in plant biotechnology. Find Jenna on Twitter @FoodBeerScience
This article originally appeared at the Cornell Alliance for Science and has been republished here with permission. Follow the Alliance for Science on Twitter @ScienceAlly