Improving Plants with a Tool Borrowed from Birds

In a rapidly changing climate landscape, the plants we rely on for food, textiles, and more face a multitude of challenges, including rising temperatures, drought, and disease. Caltech's Gözde Demirer, the Clare Boothe Luce Assistant Professor of Chemical Engineering, uses genetic engineering tools to make crops more resilient to such threats and enhance plant health. Now, she and a team of Caltech researchers have found a new solution to an old problem in an unlikely source: the zebra finch.

"For decades, plant engineering has largely relied on delivering DNA and hoping it lands in a useful place. We took inspiration from nature and turned a genetic element from a bird into a precise genome-writing system for plants," says Demirer, who is the corresponding author on a paper describing the team's findings published June 19 in Nature Biotechnology. "That shift from random insertion toward controlled genome installation could fundamentally expand how we design crops, study plant biology, and build plant-based technologies."

The DNA of living organisms provides instructions that tell them what to do and how to do it. These instructions come in the form of genes, which dictate plant traits, such as how tall a plant will grow. With the tools of genetic engineering, it is possible to enhance organisms by giving them new genes; a plant can be protected from thermal stress, for example, if it is given a gene with instructions that help it produce molecules that protect against heat.

For decades, researchers added new genes to plants using a soil bacterium Agrobacterium tumefaciens, which acts as a carrier for the genes and inserts them into a plant's genome. However, where the gene lands is random, so it may interrupt the function of a gene the plant needs or behave unpredictably. More precise tools such as CRISPR emerged in the early 2010s, but they still struggle to insert large DNA sequences accurately and efficiently in plants. So Demirer and her team turned to retrotransposons, genetic elements that can "copy and paste" new instructions efficiently to control cellular processes.

The R2 retrotransposon, a mobile genetic element found in many multicellular animals such as insects, crustaceans, and birds, uses the protein it encodes to copy cargo RNA into DNA directly at the target site in the genome. While researchers have turned them into a powerful gene-insertion tool in mammalian cells, whether the machinery could be made to work in plants was unknown.

After screening R2 editing functions in silk moths, white-throated sparrows, and zebra finches, and testing them in leaves, seedlings, and protoplasts ("naked" plant cells that have had their rigid cell walls removed), the researchers found the zebra finch R2 system to be most efficient at delivering engineered payloads into the plants.

"For the first time, a protein native to animal genomes inserted DNA inside a plant and with far greater efficiency than existing methods," explains Kimberley Muchenje, a graduate student in Demirer's lab and lead author of the new paper.

Plant genome engineering often requires the installation of not one gene but several genes, and those genes must be precisely placed in regions of the genome that are permissive to their robust expression with minimal disruption of other functions, she says.

"The R2 editor system we developed makes these goals possible in a single step," Muchenje says. In a proof-of-concept experiment, the team used the R2 system to install a three-enzyme pathway that produced red betalain pigment in a Nicotiana benthamiana leaf, a plant in the tobacco family that is typically green.

"Genes delivered this way remain active throughout our experiments with no sign of silencing, indicating that this site in the genome welcomes new genes rather than suppressing them," Muchenje notes.

The R2 editor system integrates genes roughly 30 times more efficiently than the widely used CRISPR-based method, making it especially useful for adding large genetic payloads, such as multigene metabolic pathways to enhance nutritional value. This means the new approach can be used to combine several beneficial traits at one targeted location in a single step rather than scattering them across the genome through multiple laborious rounds of editor delivery and insertion, solving a long-standing problem in plant engineering.

"Plant genome engineering has had a persistent tradeoff: We could either insert DNA efficiently or place it precisely, but rarely both, especially for large genetic payloads," Demirer says. "This work begins to break that tradeoff."

More broadly, the researchers say their study shows that the molecular machinery of one kingdom of nature can be borrowed to solve a problem in another, turning a mobile element from a bird into a precise tool for plants. While results shown so far come from transient experiments, future work will focus on refining the system to engineer crops with complex traits, opening doors to improved plants for food security, sustainable biomanufacturing, and agriculture under a changing climate.

"What excites me most is not just that we inserted genes into plants but that we showed it is possible to install complex genetic instructions into a targeted genomic address with a predictable output," Demirer says. "Biology increasingly depends on coordinating multiple genes at once, and technologies for reliable targeted DNA addition have been a missing piece for plant engineering."

The Nature Biotechnology paper is titled "Optimized R2 retroelement complexes for DNA insertion into plant genomes." Additional Caltech authors and Demirer lab members are postdoctoral scholar research associate Carl L. McCombe, prior lab manager Tufan Oz, and graduate students Yunqing Wang and Eugene Li. Amelia Saffron, a Caltech undergraduate who was a student researcher in the Demirer lab during the 2024–25 academic year, is also an author on the paper. Funding in support of the work was provided by Caltech start-up funds, the Caltech Space-Health Innovation Fund, the Henry Luce Foundation, the Shurl and Kay Curci Foundation, and the Resnick Sustainability Institute.