RNA offers distinct advantages for molecular self-assembly as a unique and programmable biomaterial.Recently,single-stranded RNA(ssRNA)origamis,capable of self-folding into defined nanostructures within a single-stran...RNA offers distinct advantages for molecular self-assembly as a unique and programmable biomaterial.Recently,single-stranded RNA(ssRNA)origamis,capable of self-folding into defined nanostructures within a single-stranded RNA molecule,are considered a promising platform for immune recognition and therapy.Here,we utilize single-stranded rod RNA origami(Rod RNA-OG)as functional nucleic acid to synthesize valence-programmed RNA structures in a one-pot manner.We discover that the polyvalent RNA origamis are resistant to RNase degradation and can be efficiently internalized by macrophages for subsequent innate immune activation,even in the absence of any external protective agents such as lipids or polymers.The valence-programmed RNA origamis thus hold great promise as novel agonists for immunotherapy.展开更多
基金supported by the National Key Research and Development Program of China(Nos.2021YFF1200300,2020YFA0909000)National Natural Science Foundation of China(Nos.22025404,32471426)+3 种基金Innovative Research Group of High-Level Local Universities in Shanghai(No.SHSMU-ZLCX20212602)Natural Science Foundation of Shanghai(No.23ZR1438700)Shanghai Municipal Health Commission(No.2022JC027)Shanghai Sailing Program(No.22YF1424400)。
文摘RNA offers distinct advantages for molecular self-assembly as a unique and programmable biomaterial.Recently,single-stranded RNA(ssRNA)origamis,capable of self-folding into defined nanostructures within a single-stranded RNA molecule,are considered a promising platform for immune recognition and therapy.Here,we utilize single-stranded rod RNA origami(Rod RNA-OG)as functional nucleic acid to synthesize valence-programmed RNA structures in a one-pot manner.We discover that the polyvalent RNA origamis are resistant to RNase degradation and can be efficiently internalized by macrophages for subsequent innate immune activation,even in the absence of any external protective agents such as lipids or polymers.The valence-programmed RNA origamis thus hold great promise as novel agonists for immunotherapy.