There is a continuing quest to rationally fabricate polymeric biomaterials with both high transfection efficiency and minimal toxicity for the emerging opportunities in small interfering RNA(siRNA)delivery.Recently,th...There is a continuing quest to rationally fabricate polymeric biomaterials with both high transfection efficiency and minimal toxicity for the emerging opportunities in small interfering RNA(siRNA)delivery.Recently,this goal was promoted highly by developing a robust and efficient strategy to facilitate polymer-mediated RNAi using natural polyphenols with multiple phenol groups that could condense siRNA effectively into negatively charged nanoparticles(NPs).Further coating of these NPs with cationic polymers of low molecular weight enabled their intracellular siRNA delivery.Inspired by the structural and functional features of natural polyphenols,we aimed to further the development of low molecular weight polycatechols as a new class of efficient and biocompatible polymers for siRNA delivery in our current study.The fabricated polycatechols have benefits of requiring only one-step fabrication toward efficient siRNA nanoformulations.Moreover,they could deliver siRNA into cells and silence target genes both in vitro and in vivo.The resulting polycatechol/siRNA formulations were also functionally competent,demonstrating a successful,profound downregulation of a proinflammatory enzyme to attenuate chronic intestinal inflammation in an intestinal injury model.This study provides a new approach in chemistry for the development of efficient synthetic polymers for therapeutic siRNA delivery.展开更多
Recent metagenomics surveys have provided insights into the marine virosphere.However,these surveys have focused solely on viruses in seawater,neglecting those associated with biofilms.By analyzing 1.75 terabases of b...Recent metagenomics surveys have provided insights into the marine virosphere.However,these surveys have focused solely on viruses in seawater,neglecting those associated with biofilms.By analyzing 1.75 terabases of biofilm metagenomic data,3974 viral sequences were identified from eight locations around the world.Over 90%of these viral sequences were not found in previously reported datasets.Comparisons between biofilm and seawater metagenomes identified viruses that are endemic to the biofilm niche.Analysis of viral sequences integrated within biofilm-derived microbial genomes revealed potential functional genes for trimeric autotransporter adhesin and polysaccharide metabolism,which may contribute to biofilm formation by the bacterial hosts.However,more than 70%of the genes could not be annotated.These findings show marine biofilms to be a reservoir of novel viruses and have enhanced our understanding of natural virus-bacteria ecosystems.展开更多
基金supported by the National Key R&D Program of China,Synthetic Biology Research(no.2019YFA0904500)the National Natural Science Foundation of China(nos.21725402 and 21774079)+1 种基金the Shanghai Municipal Science and Technology Commission(no.17XD1401600)the Guangdong Innovative and Entrepreneurial Research Team Program(no.2016ZT06C322).
文摘There is a continuing quest to rationally fabricate polymeric biomaterials with both high transfection efficiency and minimal toxicity for the emerging opportunities in small interfering RNA(siRNA)delivery.Recently,this goal was promoted highly by developing a robust and efficient strategy to facilitate polymer-mediated RNAi using natural polyphenols with multiple phenol groups that could condense siRNA effectively into negatively charged nanoparticles(NPs).Further coating of these NPs with cationic polymers of low molecular weight enabled their intracellular siRNA delivery.Inspired by the structural and functional features of natural polyphenols,we aimed to further the development of low molecular weight polycatechols as a new class of efficient and biocompatible polymers for siRNA delivery in our current study.The fabricated polycatechols have benefits of requiring only one-step fabrication toward efficient siRNA nanoformulations.Moreover,they could deliver siRNA into cells and silence target genes both in vitro and in vivo.The resulting polycatechol/siRNA formulations were also functionally competent,demonstrating a successful,profound downregulation of a proinflammatory enzyme to attenuate chronic intestinal inflammation in an intestinal injury model.This study provides a new approach in chemistry for the development of efficient synthetic polymers for therapeutic siRNA delivery.
基金The authors are grateful to a grant from the National Key Research and Development Program of China(2018YFC0310600)two grants from Ocean University of China(841912035 and 842041010)to W.Z+1 种基金The authors are also grateful to a grant from China Ocean Mineral Resources Research and Development Association(DY135-B2-03)a grant from the Hong Kong Branch of South Marine Science and Engineering Guangdong Laboratory(SMSEGL20SC01)to P.Y.Q.
文摘Recent metagenomics surveys have provided insights into the marine virosphere.However,these surveys have focused solely on viruses in seawater,neglecting those associated with biofilms.By analyzing 1.75 terabases of biofilm metagenomic data,3974 viral sequences were identified from eight locations around the world.Over 90%of these viral sequences were not found in previously reported datasets.Comparisons between biofilm and seawater metagenomes identified viruses that are endemic to the biofilm niche.Analysis of viral sequences integrated within biofilm-derived microbial genomes revealed potential functional genes for trimeric autotransporter adhesin and polysaccharide metabolism,which may contribute to biofilm formation by the bacterial hosts.However,more than 70%of the genes could not be annotated.These findings show marine biofilms to be a reservoir of novel viruses and have enhanced our understanding of natural virus-bacteria ecosystems.
