When he was younger, Junwei Ji would often spend summer holidays in a cornfield with his father, a maize breeder, helping with the hard work of manually pollinating the plants to promote the best characteristics and achieve the biggest yield.
Now Ji is building a biotechnology company using gene editing to introduce new traits into crops instead, a technology that could help tackle issues around food security and sustainability.
Ji is the co-founder of Cytotrait, which is developing a way of reprogramming chloroplast and mitochondrial genomes that could improve crop yields, increase pest or disease resistance and other useful traits.
His PhD research on establishing an efficient DNA mutagenesis method in plant chloroplast genomes, led to the Mutant Organelle Selection System (MOSS) technology being used by Cytotrait to enable the introduction of genes and gene edits into organelles. This quickly generates homoplasmy, so that every organelle of a cell or plant contains the desired gene or edit. The company says this allows the engineering of traits with localised and high-level expression, with many thousand copies of the gene per cell.
Earlier this year the company, a spinout company from The University of Manchester, UK, announced it had closed a £3m seed funding round which will allow it to build on the early data from its MOSS technology. It plans to use the seed funding for new research targeting wheat, maize, potato and canola in European and North American markets. This will see MOSS used to explore potential applications such as enhancements in yield and resilience, or the ability to drive more sustainable practices through improved carbon sequestration.
Cytotrait was previously awarded just under £500,000 in funding from the Advanced Research and Invention Agency (ARIA) to develop reliable hybrid seed production in wheat.
While much of the attention in recent years has been on gene editing with CRISPR, Ji (above) points to another set of important genomes in the same plant cell in the form of chloroplasts and the mitochondria.
These are important for plant photosynthesis and respiration, but until now there has been no efficient method to improve those genomes, he said.
“Our research aims to develop an efficient tool to improve that genome,” he said. The challenge here is to ensure that only the genome copies harbouring the edited genes are propagated which can be extremely challenging in chloroplasts and mitochondria because they can contain thousands of copies per cell. “We target the unedited ones and remove them, then only allow the edited one to propagate in the cell,” Ji explains.
This is different from the work done with something like CRISPR tool in the nucleus, which doesn’t require such specialised selection. And whereas each species has very different dynamic genomes in the nucleus, when it comes to chloroplasts and mitochondria, they are much simpler and highly conserved even across different crop species.
“If we can locate a good gene target and we improve it, very likely the mechanics is applicable to multiple different crop species and we won't interfere with what other people are doing, we can be a kind of additive to other people's traits or improvements. So, we think that we will find a unique place in the market using our special editing,” Ji told C&I.
The technology opens up the potential for various improvements to crops. One of the most obvious is yield, for example by allowing wheat to add more starch into each grain. Other modifications can tackle threats to yields. One wheat trait is called ‘stay green’ which allows plants to cope better with drought or heat; a heat wave at the wrong time can accelerate the leaf browning and shorten the time the wheat has to get more starch into the grain. In 2020 there was a 40% yield loss because of a heat wave that hit during a development stage for wheat called the grain filling stage that only lasts for about four weeks, Ji said.
Cytotrait is targeting the chloroplast to try to solve this problem to allow wheat to stay green for a longer time and recover better after a heat wave.
Ji said modifications using Cytotrait’s technology can sit alongside the work of others. “If you think, the final product is the seeds, the variety. And if I use an analogy like an EV, electric vehicle, so it's a car, but all the components actually come from all different suppliers,” he says.
The first step is to establish the MOSS technology in wheat and start to deliver the right modifications; after that the plan is to move into different crops and prove the value of the technology.
The company was spun out with support from the University of Manchester Innovation Factory, the university’s technology transfer office.