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
Oncolytic viruses(OVs)are at the forefront of biologicals for cancer treatment.They represent a diverse landscape of naturally occurring viral strains and genetically modified viruses that,either as single agents or a...Oncolytic viruses(OVs)are at the forefront of biologicals for cancer treatment.They represent a diverse landscape of naturally occurring viral strains and genetically modified viruses that,either as single agents or as part of combination therapies,are being evaluated in preclinical and clinical settings.As the field gains momentum,the research on OVs has been shifting efforts to expand our understanding of the complex interplay between the virus,the tumor and the immune system,with the aim of rationally designing more efficient therapeutic interventions.Nowadays,the potential of an OV platform is no longer defined exclusively by the targeted replication and cancer cell killing capacities of the virus,but by its contribution as an immunostimulator,triggering the transformation of the immunosuppressive tumor microenvironment(TME)into a place where innate and adaptive immunity players can efficiently engage and lead the development of tumor-specific long-term memory responses.Here we review the immune mechanisms and host responses induced by ssRNA(-)(negative-sense single-stranded RNA)viruses as OV platforms.We focus on two ssRNA(-)OV candidates:Newcastle disease virus(NDV),an avian paramyxovirus with one of the longest histories of utilization as an OV,and influenza A(IAV)virus,a well-characterized human pathogen with extraordinary immunostimulatory capacities that is steadily advancing as an OV candidate through the development of recombinant IAV attenuated platforms.展开更多
Viral diseases have been studied in-depth for reducing quality,yield,health and longevity of the fruit,to highlight the economic losses.Positive-sense single-stranded RNA viruses are more devastating among all viruses...Viral diseases have been studied in-depth for reducing quality,yield,health and longevity of the fruit,to highlight the economic losses.Positive-sense single-stranded RNA viruses are more devastating among all viruses that infect fruit trees.One of the best examples is papaya ringspot virus(PRSV).It belongs to the genus Potyvirus and it is limited to cause diseases on the family Chenopodiaceae,Cucurbitaceae and Caricaceae.This virus has a serious threat to the production of papaya,which is famous for its high nutritional and pharmaceutical values.The plant parts such as leaves,latex,seeds,fruits,bark,peel and roots may contain the biological compound that can be isolated and used in pharmaceutical industries as a disease control.Viral disease symptoms consist of vein clearing and yellowing of young leaves.Distinctive ring spot patterns with concentric rings and spots on fruit reduce its quality and taste.The virus has two major strains P and W.The former cause disease in papaya and cucurbits while the later one in papaya.Virion comprises 94.4%protein,including a 36 kDa coat protein which is a component responsible for a non-persistent transmission through aphids,and 5.5%nucleic acid.Cross protection,development of transgenic crops,exploring the resistant sources and induction of pathogen derived resistance have been recorded as effective management of PRSV.Along with these practices reduced aphid population through insecticides and plant extracts have been found ecofriendly approaches to minimize the disease incidence.Adoption of transgenic crops is a big challenge for the success of disease resistant papaya crops.The aim of this review is to understand the genomic nature of PRSV,detection methods and the different advanced control methods.This review article will be helpful in developing the best management strategies for controlling PRSV.展开更多
We have determined the binding strengths between ribonucleotides of adenine(A),guanine(G),uracil(U),and cytosine(C)in homogeneous single-stranded ribonucleic acids(ssRNAs)and homo-decapeptides consisting of 20 common ...We have determined the binding strengths between ribonucleotides of adenine(A),guanine(G),uracil(U),and cytosine(C)in homogeneous single-stranded ribonucleic acids(ssRNAs)and homo-decapeptides consisting of 20 common amino acids.We use a bead-based fluorescence assay for these measurements in which decapeptides are immobilized on the bead surface and ssRNAs are in solutions.The results provide a molecular basis for analyzing selectivity,specificity,and polymorphisms of amino-acid–ribonucleotide interactions.Comparative analyses of the distribution of the binding energies reveal unique binding strength patterns assignable to each pair of amino acid and ribonucleotide originating from the chemical structures.Pronounced favorable(such as Arg–G)and unfavorable(such as Met–U)binding interactions can be identified in selected groups of amino acid and ribonucleotide pairs that could provide basis to elucidate energetics of amino-acid–ribonucleotide interactions.Such interaction selectivity,specificity,and polymorphism manifest the contributions from RNA backbone,RNA bases,as well as main chain and side chain of the amino acids.Such characteristics in peptide–RNA interactions might be helpful for understanding the mechanism of protein–RNA specific recognition and the design of RNA nano-delivery systems based on peptides and their derivatives.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.
基金This work was partly supported by NCI grant R01CA229818 to Garcia-Sastre A.
文摘Oncolytic viruses(OVs)are at the forefront of biologicals for cancer treatment.They represent a diverse landscape of naturally occurring viral strains and genetically modified viruses that,either as single agents or as part of combination therapies,are being evaluated in preclinical and clinical settings.As the field gains momentum,the research on OVs has been shifting efforts to expand our understanding of the complex interplay between the virus,the tumor and the immune system,with the aim of rationally designing more efficient therapeutic interventions.Nowadays,the potential of an OV platform is no longer defined exclusively by the targeted replication and cancer cell killing capacities of the virus,but by its contribution as an immunostimulator,triggering the transformation of the immunosuppressive tumor microenvironment(TME)into a place where innate and adaptive immunity players can efficiently engage and lead the development of tumor-specific long-term memory responses.Here we review the immune mechanisms and host responses induced by ssRNA(-)(negative-sense single-stranded RNA)viruses as OV platforms.We focus on two ssRNA(-)OV candidates:Newcastle disease virus(NDV),an avian paramyxovirus with one of the longest histories of utilization as an OV,and influenza A(IAV)virus,a well-characterized human pathogen with extraordinary immunostimulatory capacities that is steadily advancing as an OV candidate through the development of recombinant IAV attenuated platforms.
文摘Viral diseases have been studied in-depth for reducing quality,yield,health and longevity of the fruit,to highlight the economic losses.Positive-sense single-stranded RNA viruses are more devastating among all viruses that infect fruit trees.One of the best examples is papaya ringspot virus(PRSV).It belongs to the genus Potyvirus and it is limited to cause diseases on the family Chenopodiaceae,Cucurbitaceae and Caricaceae.This virus has a serious threat to the production of papaya,which is famous for its high nutritional and pharmaceutical values.The plant parts such as leaves,latex,seeds,fruits,bark,peel and roots may contain the biological compound that can be isolated and used in pharmaceutical industries as a disease control.Viral disease symptoms consist of vein clearing and yellowing of young leaves.Distinctive ring spot patterns with concentric rings and spots on fruit reduce its quality and taste.The virus has two major strains P and W.The former cause disease in papaya and cucurbits while the later one in papaya.Virion comprises 94.4%protein,including a 36 kDa coat protein which is a component responsible for a non-persistent transmission through aphids,and 5.5%nucleic acid.Cross protection,development of transgenic crops,exploring the resistant sources and induction of pathogen derived resistance have been recorded as effective management of PRSV.Along with these practices reduced aphid population through insecticides and plant extracts have been found ecofriendly approaches to minimize the disease incidence.Adoption of transgenic crops is a big challenge for the success of disease resistant papaya crops.The aim of this review is to understand the genomic nature of PRSV,detection methods and the different advanced control methods.This review article will be helpful in developing the best management strategies for controlling PRSV.
基金supported by the National Natural Science Foundation of China(Nos.21721002,32101130,and 31971295)Financial support from the Strategic Priority Research Program of Chinese Academy of Sciences(No.XDB36000000)is also gratefully acknowledged.
文摘We have determined the binding strengths between ribonucleotides of adenine(A),guanine(G),uracil(U),and cytosine(C)in homogeneous single-stranded ribonucleic acids(ssRNAs)and homo-decapeptides consisting of 20 common amino acids.We use a bead-based fluorescence assay for these measurements in which decapeptides are immobilized on the bead surface and ssRNAs are in solutions.The results provide a molecular basis for analyzing selectivity,specificity,and polymorphisms of amino-acid–ribonucleotide interactions.Comparative analyses of the distribution of the binding energies reveal unique binding strength patterns assignable to each pair of amino acid and ribonucleotide originating from the chemical structures.Pronounced favorable(such as Arg–G)and unfavorable(such as Met–U)binding interactions can be identified in selected groups of amino acid and ribonucleotide pairs that could provide basis to elucidate energetics of amino-acid–ribonucleotide interactions.Such interaction selectivity,specificity,and polymorphism manifest the contributions from RNA backbone,RNA bases,as well as main chain and side chain of the amino acids.Such characteristics in peptide–RNA interactions might be helpful for understanding the mechanism of protein–RNA specific recognition and the design of RNA nano-delivery systems based on peptides and their derivatives.
