A gene and drug co-delivery application helps to solve the short life disadvantage of RNA drug

Novel green technology RNA pesticide has been put forward as a promising method for plant protection, but the instability and short life disadvantage of double-stranded RNA (dsRNA) seriously constrain the commercialization process of RNA pesticide. Herein, a star polycation (SPc)-based gene/drug delivery system was constructed for co-delivering hemocytin (hem) dsRNA and botanical pesticide matrine to develop a novel multicomponent nano-pesticide for achieving sequential bioactivity against devastating green peach aphids. The self-assembled matrine/SPc complex could be further complexed with dsRNA through electrostatic interaction and hydrogen bond to form nano-sized matrine/SPc/dsRNA complex. The screened dshem fragment led to efficient gene silencing and high mortality rate through SPc-based topical application, and the main lethal mechanism was through down-regulating hem gene to result in severe bacterial infection. The dshem fragment was successfully expressed in pET28-BL21 (DE3) RNaseIII- system to prepare matrine/SPc/dshem complex. Both initial acting time and persistence of matrine/SPc/dshem complex were remarkably improved in field, which overcame the short life disadvantage of dshem and slow-acting property of matrine simultaneously. To our knowledge, it is the first success to co-deliver dsRNA and drug by nanoparticle-mediated delivery system in agricultural field.