Synthetic antigen-encoding mRNA plays an increasingly significant role in tumor vaccine technology owing to its antigen-specific immune-activation. However, its immune efficacy is challenged by inferior delivery effic...Synthetic antigen-encoding mRNA plays an increasingly significant role in tumor vaccine technology owing to its antigen-specific immune-activation. However, its immune efficacy is challenged by inferior delivery efficiency and demand for suitable adjuvants. Here, we develop a novel mRNA nanovaccine based on a multifunctional nanocapsule, which is a dual-adjuvant formulation composed of cytosine-phosphateguanine motifs loaded tetrahedral framework nucleic acid(CpG-tFNA) and an immunopeptide murine β-defensin 2(mDF2β). This m RNA nanovaccine successfully achieves intracellular delivery, antigen expression and presentation of dendritic cells, and proliferation of antigen-specific T cells. In a tumor prophylactic vaccination model, it exerts an excellent inhibitory effect on lymphoma occurrence through cellular immunity. This mRNA nanovaccine has promising prophylactic applications in tumors and many other diseases.展开更多
Segmental bone defects,stemming from trauma,infection,and tumors,pose formidable clinical challenges.Traditional bone repair materials,such as autologous and allogeneic bone grafts,grapple with limitations including s...Segmental bone defects,stemming from trauma,infection,and tumors,pose formidable clinical challenges.Traditional bone repair materials,such as autologous and allogeneic bone grafts,grapple with limitations including source scarcity and immune rejection risks.The advent of nucleic acid nanotechnology,particularly the use of DNA hydrogels in tissue engineering,presents a promising solution,attributed to their biocompatibility,biodegradability,and programmability.However,these hydrogels,typically hindered by high gelation temperatures(~46◦C)and high construction costs,limit cell encapsulation and broader application.Our research introduces a novel polymer-modified DNA hydrogel,developed using nucleic acid nanotechnology,which gels at a more biocompatible temperature of 37◦C and is cost-effective.This hydrogel then incorporates tetrahedral Framework Nucleic Acid(tFNA)to enhance osteogenic mineralization.Furthermore,considering the modifiability of tFNA,we modified its chains with Aptamer02(Apt02),an aptamer known to foster angiogenesis.This dual approach significantly accelerates osteogenic differentiation in bone marrow stromal cells(BMSCs)and angiogenesis in human umbilical vein endothelial cells(HUVECs),with cell sequencing confirming their targeting efficacy,respectively.In vivo experiments in rats with critical-size cranial bone defects demonstrate their effectiveness in enhancing new bone formation.This innovation not only offers a viable solution for repairing segmental bone defects but also opens avenues for future advancements in bone organoids construction,marking a significant advancement in tissue engineering and regenerative medicine.展开更多
Periodontitis is a common disease that causes periodontium defects and tooth loss.Controlling inflammation and tissue regeneration are two key strategies in the treatment of periodontitis.Tetrahedral framework nucleic...Periodontitis is a common disease that causes periodontium defects and tooth loss.Controlling inflammation and tissue regeneration are two key strategies in the treatment of periodontitis.Tetrahedral framework nucleic acids can modulate multiple biological behaviors,and thus,their biological applications have been widely explored.In this study,we investigated the effect of tFNAs on periodontium under inflammatory conditions.Lipopolysaccharide and silk ligature were used to induce inflammation in vivo and in vitro.The results displayed that tFNAs decreased the release of pro-inflammatory cytokines and levels of cellular reactive oxygen species in periodontal ligament stem cells,which promoted osteogenic differentiation.Furthermore,animal experiments showed that tFNAs ameliorated the inflammation of the periodontium and protect periodontal tissue,especially reducing alveolar bone absorption by decreasing inflammatory infiltration and inhibiting osteoclast formation.These findings suggest that tFNAs can significantly improve the therapeutic effect of periodontitis and have the great potential significance in the field of periodontal tissue regeneration.展开更多
The field of regenerative medicine faces a notable challenge in terms of the regeneration of articular cartilage.Without proper treatment,it can lead to osteoarthritis.Based on the research findings,human umbilical co...The field of regenerative medicine faces a notable challenge in terms of the regeneration of articular cartilage.Without proper treatment,it can lead to osteoarthritis.Based on the research findings,human umbilical cord mesenchymal stem cells(hUMSCs)are considered an excellent choice for regenerating cartilage.However,there is still a lack of suitable biomaterials to control their ability to self-renew and differentiate.To address this issue,in this study using tetrahedral framework nucleic acids(tFNAs)as a new method in an in vitro culture setting to manage the behaviour of hUMSCs was proposed.Then,the influence of tFNAs on hUMSC proliferation,migration and chondrogenic differentiation was explored by combining bioinformatics methods.In addition,a variety of molecular biology techniques have been used to investigate deep molecular mechanisms.Relevant results demonstrated that tFNAs can affect the transcriptome and multiple signalling pathways of hUMSCs,among which the PI3K/Akt pathway is significantly activated.Furthermore,tFNAs can regulate the expression levels of multiple proteins(GSK3β,RhoA and mTOR)downstream of the PI3K-Akt axis to further enhance cell proliferation,migration and hUMSC chondrogenic differentiation.tFNAs provide new insight into enhancing the chondrogenic potential of hUMSCs,which exhibits promising potential for future utilization within the domains of AC regeneration and clinical treatment.展开更多
基金supported by National Key R&D Program of China (No. 2019YFA0110600)National Natural Science Foundation of China (No. 81970916)+2 种基金Sichuan Province Youth Science and Technology Innovation Team (No. 2022JDTD0021)Research Funding from West China School/Hospital of Stomatology Sichuan University (No. RCDWJS2021-20)China Postdoctoral Science Foundation (No. 2022TQ0381)。
文摘Synthetic antigen-encoding mRNA plays an increasingly significant role in tumor vaccine technology owing to its antigen-specific immune-activation. However, its immune efficacy is challenged by inferior delivery efficiency and demand for suitable adjuvants. Here, we develop a novel mRNA nanovaccine based on a multifunctional nanocapsule, which is a dual-adjuvant formulation composed of cytosine-phosphateguanine motifs loaded tetrahedral framework nucleic acid(CpG-tFNA) and an immunopeptide murine β-defensin 2(mDF2β). This m RNA nanovaccine successfully achieves intracellular delivery, antigen expression and presentation of dendritic cells, and proliferation of antigen-specific T cells. In a tumor prophylactic vaccination model, it exerts an excellent inhibitory effect on lymphoma occurrence through cellular immunity. This mRNA nanovaccine has promising prophylactic applications in tumors and many other diseases.
基金supported by National Natural Science Foundation of China(82230071,82172098)Integrated Project of Major Research Plan of National Natural Science Foundation of China(92249303)+1 种基金Shanghai Committee of Science and Technology(23141900600,Laboratory Animal Research Project)Shanghai Clinical Research Plan of SHDC2023CRT01.
文摘Segmental bone defects,stemming from trauma,infection,and tumors,pose formidable clinical challenges.Traditional bone repair materials,such as autologous and allogeneic bone grafts,grapple with limitations including source scarcity and immune rejection risks.The advent of nucleic acid nanotechnology,particularly the use of DNA hydrogels in tissue engineering,presents a promising solution,attributed to their biocompatibility,biodegradability,and programmability.However,these hydrogels,typically hindered by high gelation temperatures(~46◦C)and high construction costs,limit cell encapsulation and broader application.Our research introduces a novel polymer-modified DNA hydrogel,developed using nucleic acid nanotechnology,which gels at a more biocompatible temperature of 37◦C and is cost-effective.This hydrogel then incorporates tetrahedral Framework Nucleic Acid(tFNA)to enhance osteogenic mineralization.Furthermore,considering the modifiability of tFNA,we modified its chains with Aptamer02(Apt02),an aptamer known to foster angiogenesis.This dual approach significantly accelerates osteogenic differentiation in bone marrow stromal cells(BMSCs)and angiogenesis in human umbilical vein endothelial cells(HUVECs),with cell sequencing confirming their targeting efficacy,respectively.In vivo experiments in rats with critical-size cranial bone defects demonstrate their effectiveness in enhancing new bone formation.This innovation not only offers a viable solution for repairing segmental bone defects but also opens avenues for future advancements in bone organoids construction,marking a significant advancement in tissue engineering and regenerative medicine.
基金This study was supported by National Key R&D Program of China(2019YFA0110600)National Natural Science Foundation of China(81970986,81771125).
文摘Periodontitis is a common disease that causes periodontium defects and tooth loss.Controlling inflammation and tissue regeneration are two key strategies in the treatment of periodontitis.Tetrahedral framework nucleic acids can modulate multiple biological behaviors,and thus,their biological applications have been widely explored.In this study,we investigated the effect of tFNAs on periodontium under inflammatory conditions.Lipopolysaccharide and silk ligature were used to induce inflammation in vivo and in vitro.The results displayed that tFNAs decreased the release of pro-inflammatory cytokines and levels of cellular reactive oxygen species in periodontal ligament stem cells,which promoted osteogenic differentiation.Furthermore,animal experiments showed that tFNAs ameliorated the inflammation of the periodontium and protect periodontal tissue,especially reducing alveolar bone absorption by decreasing inflammatory infiltration and inhibiting osteoclast formation.These findings suggest that tFNAs can significantly improve the therapeutic effect of periodontitis and have the great potential significance in the field of periodontal tissue regeneration.
基金supported by the National Key R&D Program of China(2019YFA0110600).
文摘The field of regenerative medicine faces a notable challenge in terms of the regeneration of articular cartilage.Without proper treatment,it can lead to osteoarthritis.Based on the research findings,human umbilical cord mesenchymal stem cells(hUMSCs)are considered an excellent choice for regenerating cartilage.However,there is still a lack of suitable biomaterials to control their ability to self-renew and differentiate.To address this issue,in this study using tetrahedral framework nucleic acids(tFNAs)as a new method in an in vitro culture setting to manage the behaviour of hUMSCs was proposed.Then,the influence of tFNAs on hUMSC proliferation,migration and chondrogenic differentiation was explored by combining bioinformatics methods.In addition,a variety of molecular biology techniques have been used to investigate deep molecular mechanisms.Relevant results demonstrated that tFNAs can affect the transcriptome and multiple signalling pathways of hUMSCs,among which the PI3K/Akt pathway is significantly activated.Furthermore,tFNAs can regulate the expression levels of multiple proteins(GSK3β,RhoA and mTOR)downstream of the PI3K-Akt axis to further enhance cell proliferation,migration and hUMSC chondrogenic differentiation.tFNAs provide new insight into enhancing the chondrogenic potential of hUMSCs,which exhibits promising potential for future utilization within the domains of AC regeneration and clinical treatment.
