CHRONIC DISEASES SUCH AS INFLAMMATORY BOWEL DISEASE, DIABETES, AND OSTEOPOROSIS AFFECT MILLIONS OF AMERICANS AND REQUIRE LONG-TERM TREATMENT WITH EXPENSIVE DRUGS THAT ARE USUALLY DELIVERED BY INJECTION. INJECTIONS ARE NOT ONLY COSTLY AND INCONVENIENT, BUT THEY ALSO DISCOURAGE PATIENTS FROM STAYING ON THEIR MEDICATIONS, WHICH CAN WORSEN HEALTH OUTCOMES AND INCREASE HEALTHCARE COSTS FOR FAMILIES AND COMMUNITIES. FINDING AFFORDABLE, SAFE, AND EASY-TO-USE ALTERNATIVES IS A CRITICAL NEED.THIS PROJECT WILL ESTABLISH PROOF-OF-CONCEPT FOR USING LETTUCE AS A PLATFORM TO PRODUCE AND DELIVER NEXT-GENERATION ORAL BIOLOGICS. LETTUCE IS ALREADY A SAFE, WIDELY CONSUMED CROP, AND IT CAN BE GROWN QUICKLY AND INEXPENSIVELY USING STANDARD AGRICULTURAL PRACTICES. WE WILL TEST NEW WAYS OF ENGINEERING LETTUCE TO PRODUCE PROTEIN-BASED MEDICINES THAT ARE PROTECTED DURING DIGESTION AND RELEASED IN THE INTESTINE WHERE THEY ARE MOST EFFECTIVE. WE WILL USE STANDARD GREENHOUSE PRACTICES TO GROW LETTUCE PLANTS THAT CONTAIN SPECIALLY DESIGNED PROTEINS, THEN EVALUATE HOW WELL THESE PROTEINS ARE MADE, HOW STABLE THEY ARE, AND WHETHER THEY REMAIN ACTIVE AFTER PASSING THROUGH SIMULATED STOMACH AND INTESTINAL CONDITIONS. BY SHOWING THAT LETTUCE CAN SERVE AS A SAFE AND EFFECTIVE CAPSULE FOR ORAL DELIVERY OF MEDICINES, THIS RESEARCH WILL LAY THE FOUNDATION FOR A NEW GENERATION OF AFFORDABLE BIOLOGICS THAT PATIENTS CAN TAKE BY MOUTH INSTEAD OF INJECTIONS. THE ULTIMATE GOAL IS TO IMPROVE HUMAN HEALTH THROUGH MORE ACCESSIBLE TREATMENTS, WHILE ALSO CREATING NEW USES FOR AGRICULTURAL CROPS THAT CAN BENEFIT FARMERS, BIOTECHNOLOGY INDUSTRIES, AND THE LARGER COMMUNITY.