Gene-silencing spray lets us modify plants without changing DNA

Don’t like the look of those roses in your garden? One day you might be able to buy a spray that changes the colour of their flowers by silencing certain genes.

Farmers may use similar gene-silencing sprays to boost yields, make their crops more nutritious, protect them from droughts and trigger ripening. The technique could let us change plant traits without altering their DNA.

“A spray can be used immediately without having to go through the years involved in development of a GM or conventionally bred crop,” says David Baulcombe at the University of Cambridge, who studies gene silencing in plants. One spray can also be used on many different varieties, he points out.

Companies like Monsanto are already developing gene-silencing sprays that get inside bugs and kill them by disabling vital genes.

Long-lasting action

Now a team at the University of Queensland in Australia has managed to achieve long-lasting gene silencing inside plant cells. They have protected tobacco plants from a virus for 20 days with a single application of a gene-silencing spray.

“We believe it offers a step change in environmentally sustainable crop protection,” says team member Neena Mitter.

The technique should allow plant traits to be altered, too, but the team has not tried this as they are focusing on crop protection.

Many other teams around the world are trying to achieve such long-lasting effects in plants. Mitter’s is the first to publish such results.

It is a very exciting result, says John Killmer of biotech startup Apse. “This could open up all kinds of plant ‘modification’ unrelated to insect and disease control.”

Gene silencing exploits a natural defence system. When viruses invade cells, the cells cut up some of the viral RNAs to make short pieces of double-stranded RNAs, which they use to recognise and destroy any RNAs with matching sequences. Without viral RNA, no viral proteins are made, so viruses cannot replicate.

RNA interference, as this often called, can be used to block production of any protein. Efforts to produce RNAi-based drugs for people have not got far because even when injected into the blood RNAs are rapidly broken down.

Next-generation defence

But many genetically modified plants work by producing gene-silencing RNAs. What is more, it has been discovered that specific genes can be shut down in some – although not all – bugs and plants simply by spraying them with small double-stranded RNAs with sequences matching the genes.

Monsanto, for instance, is developing RNAi sprays that kill pests. Its spray targeting the varroa mites contributing to the woes of bees is now entering the final stages of development, the company revealed on 5 January.

One challenge with the spray approach is that the effects on plants last only a few days because unprotected RNAs soon break down. Farmers will not want to apply expensive sprays this often.

In experiments with tobacco plants, Mitter’s team has now shown it can make the protective effect last at least 20 days. This was achieved by combining the RNAs with clay nanoparticles developed by her colleague Gordon Xu.

The positively charged clay nanoparticles, made of stacked sheets of common minerals such as magnesium chloride, bind and protect the negatively charged RNAs. Over time, the clay particles react with carbon dioxide and break down, slowly releasing the RNAs.

Lack of options

Plant viruses are a huge problem for farmers around the world, and no existing treatments target them directly. Farmers must either grow resistant varieties, if they exist, or try to kill the organisms that spread plant viruses, such as aphids.

So if the antiviral spray works as well in field tests on crop plants, there could be huge demand. “We do believe it will be commercially viable,” Mitter says.

The biggest obstacle is cost – while clay nanoparticles are cheap to make, making RNA is expensive. A few years ago, it would have cost over $100,000 to make the gram or so needed to treat a small field. But this is changing fast. Killmer’s company Apse aims to mass-produce RNAs for under $2 per gram.

Gene-silencing sprays should be far safer than ordinary pesticides. RNAs cannot pass through human skin and are rapidly broken down in the body.

While one 2012 study claimed some of the plant RNAs present in the food we eat already could affect human genes, several follow-up studies have found no evidence of any such effect.

Flexible and safe?

Combining RNAs with clay nanoparticles should not make them any less safe, Baulcombe says. “I would not have any concerns about that at all.”

There is a risk that RNAi sprays could affect non-target organisms – such as worms or fungi in soil – if their DNA contains matching sequences. In theory, target organisms could also evolve resistance by changing their DNA.

The great advantage of gene silencing is that by altering the sequence of the RNAs it should be possible to avoid non-target effects and overcome most forms of resistance.

The technology looks set to divide those who oppose genetically modified crops, with at least a few in the anti-GM camp welcoming the new approach. “I have had organic growers call me up and tell me to hurry up with the technology,” says Killmer.

Gene-silencing sprays are not the only new kid on the block. Other biologists are developing trait-altering sprays based on plant signalling molecules.

Journal reference: Nature Plants, DOI: 10.1038/nplants.2016.207