Penn Dental researchers have engineered lettuce to produce functional GLP-1 peptides, a potential breakthrough for making diabetes and obesity drugs cheaper, easier to take, and gentler on patients.
Professor Henry Daniell and his team have genetically engineered lettuce chloroplasts, grown in a greenhouse on the Pennovation Works complex, to produce two FDA-approved GLP-1 peptides, exenatide and lixisenatide, in a form that can be delivered orally. The findings, published in Plant Biotechnology Journal, point toward a future where patients could take their medication as a plant-based pill rather than a syringe.
"People don't want injections, even just one a week. They want pills," said Prof. Henry Daniell, Penn School of Dental Medicine. The challenge with oral delivery of peptide drugs has always been the digestive system: stomach acid and enzymes break them down before they can reach the bloodstream. Even the recently approved oral form of semaglutide requires patients to fast, drink precisely 4 oz of water, and wait 30 minutes before eating, and side effects remain common. Daniell's plant-based approach sidesteps these obstacles entirely. Human enzymes can't digest plant cells, but gut bacteria can — releasing the peptides precisely where they need to be absorbed.
The lettuce approach is different because plant cell walls protect peptides from stomach acid and premature breakdown, chloroplasts perform the chemical modifications needed to make the peptides functional so no synthetic processing is required, and production is simpler, and cheaper, than conventional pharmaceutical manufacturing
