Farmers have tinkered with crop genomes for thousands of years, slowly improving crop traits and meticulously saving seeds to propagate cultivars the next season.
In the 1950s, governments worldwide attempted to find significant, peaceful uses for their atomic energy programs after World War II, and to bring atomic energy and experimentation into the lives of ordinary citizens. They bludgeoned the genomes of crops like maize, grapefruit, and peppermint with gamma radiation, and some interesting and useful crops grew from those mutated seeds. Soon, scientists were bathing seeds in harsh chemicals and using other physical methods (ion beams, X-rays) to drive mutation. Then, the era of genomic DNA editing brought us genetic modification, where new genes could be added to crop genomes from other species, like flowers, bacteria, or fish. Now RNA technologies, CRISPR, and artificial intelligence are being used.
With the development of Pfizer’s COVID-19 mRNA vaccine, RNA technology has been dominating the news cycle. RNA is the less well-known cousin of DNA. DNA is a double-stranded molecule that resides in the nucleus of every cell, while RNA is a single-stranded “messenger” molecule. DNA can be thought of as like an original hard cover book, protected by the nucleus. Whereas RNA is like a Xerox copy. Many messages can be cheaply made, sent out unprotected into the cell’s cytoplasm, and disposed of after the message is delivered. Since these messages are naked, they are vulnerable and can be interfered with to dial down the expression or action of certain genes. RNA interference (RNAi) is a natural gene-silencing mechanism that is triggered by the presence of (irregular) double-stranded RNA (dsRNA).
Gene-editing technologies do not introduce foreign DNA into an organism, but rather they tinker with the expression of the genes, turning off harmful ones and turning on (or up) helpful ones.
The Arctic Apple is one example of an approved GMO that has been engineered with RNAi to reduce polyphenol oxidase (PPO) enzymes responsible for browning apple flesh after bruising. Varieties that have received U.S. approval include Arctic Golden (called GD743) and Arctic Granny (GS784) in 2015, and Arctic Fuji (NF872) in 2016. The genetically modified Innate potato, developed by J. R. Simplot Company, was approved by the U.S. Department of Agriculture in 2014 and the U.S. Food and Drug Administration in 2015. It is also designed with RNAi technology to resist blackspot bruising and browning and to contain less of the amino acid asparagine that turns into cancerous acrylamide during the frying of potatoes.
Simplot was not the first company to discover the power of RNA. A decade ago, Monsanto discovered that RNA could directly modify the expression of plant genes.
Monsanto (now Bayer) and other seed companies have started employing the extraordinary power of RNA interference (RNAi) in spray form, to knockdown a destructive insect’s genes, effectively killing them by shutting off genes that they need to survive. The RNAi spray, can directly genetically modify plants, by entering into the plant’s cells through the leaves.
They also took over a company called Beeologics, which had found a way to introduce RNA into sugar water that bees feed on in order to kill a parasitic mite that infests hives. That company also came up with a much cheaper way to make RNA, which has traditionally been very expensive to produce.
Once the dsRNA is ingested by insects, it is thought to be taken up by midgut cells and processed by the native RNAi machinery. The RNAi pathway is initiated by cleavage of double stranded RNA into short RNAs that can act as interfering molecules, by an enzyme appropriately called Dicer. This interference or suppression can cause lethality if the target mRNA encodes a protein for an essential function within the insect.
Monsanto had paid $30 million for access to the RNA interference know-how (and patents) held by the biotech companies Alnylam, and Tekmira. Additionally, they are the financial backer of a 15-person company called Preceres, where robotic mixers stir RNA together with coatings of specialized nanoparticles to deliver this miraculous technology.
The U.S. Environmental Protection Agency has registered RNAi products containing this new and innovative plant-incorporated protectant (PIP) called SMARTSTAX PRO, which will help U.S. farmers control corn rootworm. The first product is DvSnf7 dsRNA in SmartStax Pro, a line of genetically modified corn seeds made in collaboration between Monsanto and Dow.
DvSnf7 dsRNA is so specific that it only affects the corn rootworm. The most novel thing about this technology is that DvSnf7 dsRNA actually silences a gene in another living organism. Rather than modifying the plant itself, it modifies its environment!!
Crops that express double-stranded RNA (dsRNA) molecules are being developed that take advantage of the endogenous RNAi machinery of target insects and can produce highly specific insecticidal oligonucleotides (siRNA) for agricultural pest control. DvSnf7 dsRNA expressed in GM maize confers protection against the western corn rootworm, a threat known as the “billion dollar pest” because of the damage it can cause.
Gene-editing techniques such as the zinc-finger nuclease (ZFN) and transcription activator-like effector nuclease (TALEN) systems, and CRISPR have all escaped USDA regulation, as the Animal and Plant Health Inspection Service (APHIS) has said that the organisms — mostly plants — do not qualify as something the agency must regulate. Yinong Yang, a plant pathologist at Penn State, engineered the common white button (Agaricus bisporus) mushroom to resist browning with CRISPR technology.
In recent years, DNA and RNA had been understood as simply a numeric sequence that can be computationally mapped, but now artificial intelligence algorithms are being developed to speed up improvements. Benson Hill Biosystems announced a new CRISPR 3.0 tool for agricultural applications, including increasing the nutritional density of crops and improving yield against stressors such as drought, among others. They plan on providing their AI tools to other companies in a partnership agreement that promises to empower companies of any size to access the most advanced tools in seed innovation without major infrastructure costs. In March 2020, they commercialized the first ultra-high protein soybeans with the potential to replace soy protein concentrate, reducing costly and water-intensive processing steps to improve the sustainability of feed and food ingredients. The high yield, high protein soy was developed through traditional breeding but used Benson Hill’s proprietary phenotyping, predictive breeding and environmental modeling algorithms to accelerate the development.
Other plant genomics innovators leveraging artificial intelligence or advanced bioinformatics — include Caribou Biosciences, Indigo, Cibus, Zymergen, Phytelligence, Roslin, and Native Traits.
These new technologies are helping us develop new crops and traits to meet the demands of an ever-growing population and the challenge of climate change, and there are bright spots with regard to a changing regulatory landscape with updated guidelines for faster approvals.