** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** PALMER AMARANTH (AMARANTHUS PALMERI) IS THE MOST SERIOUS WEED IN COTTON MAINLY DUE TO ITS RAPID EVOLUTION OF RESISTANCE TO MOST MECHANISMS OF ACTION (MOA) AND MASSIVE SEED PRODUCTION THAT MAKE CONTROL OF ITS POPULATIONS CHALLENGING. THEREFORE, THERE IS AN URGENT NEED TO DEVELOP INNOVATIVE STRATEGIES THAT NOT ONLY PREVENT INTERFERENCE WITH THE CROP BUT MORE IMPORTANTLY THAT REDUCE WEED POPULATION GROWTH. NEW MOLECULAR BIOLOGY TECHNIQUES CAN BE INCORPORATED INTO INTEGRATED PROGRAMS TO ENSURE THE LONG-TERM VIABILITY OF WEED MANAGEMENT STRATEGIES. RNAI TECHNOLOGY HAS THE POTENTIAL TO GENERATE CONTROL SOLUTIONS THAT COMPLEMENT EXISTING WEED MANAGEMENT APPROACHES. ALTHOUGH THIS TECHNOLOGY HAS BEEN WIDELY INVESTIGATED TO REDUCE THE ECONOMIC IMPACT OF OTHER PESTS, VERY LIMITED RESEARCH HAS BEEN CONDUCTED FOR WEED CONTROL WHICH HAS MAINLY FOCUSED ON SUBSTITUTION OF HERBICIDES. NO WORK HAS BEEN DONE TO DEVELOP RNAI PROGRAMS THAT TARGET GROWTH AND FITNESS TRAITS SUCH AS PLANT HEIGHT AND INTERNODE ELONGATION, FLOWERING, AND SEED DORMANCY. GENETIC AND PHYSIOLOGICAL PATHWAYS CONTROLLING THOSE TRAITS HAVE BEEN WIDELY CHARACTERIZED AND ARE NOW WELL KNOWN. WE ALSO HAVE IDENTIFIED NEW NON-DRUGGABLE TARGETS THAT ARE CRITICAL FOR PLANT SURVIVAL AND CAN BE USED FOR WEED CONTROL. REDUCING THE EXPRESSION OF GENES RELATED TO THOSE PROCESSES WITH RNAI TECHNOLOGY WILL HELP REDUCE THE SURVIVAL, FITNESS, AND SEED PRODUCTION OF PALMER AMARANTH ESCAPING HERBICIDE CONTROL IN COTTON FIELDS. WE PROPOSE: 1) TO DESIGN RNAI SYSTEMS TO SILENCE TARGET GENES IN PALMER AMARANTH, 2) TO CHARACTERIZE THE EFFECTS OF THOSE RNAI SYSTEMS ON COTTON, AND 3) TO DETERMINE DSRNA STABILITY AND PERSISTENCE WHEN EXPOSED TO DIFFERENT POTENTIAL ABIOTIC AND BIOTIC DEGRADATION AGENTS. THE PROPOSED RESEARCH WILL SET THE BASES TO REGAIN CONTROL OF HERBICIDE RESISTANT WEEDS IN COTTON WHILE PROMOTING NUMEROUS BENEFITS TO COTTON GROWERS BY REDUCING RELIANCE ON HERBICIDES.