Nucleic acid-based bioactive substances have recently emerged as a new class of nextgeneration therapeutics, but their development has been limited by their relatively weakdelivery into target cells. Cationic liposome...Nucleic acid-based bioactive substances have recently emerged as a new class of nextgeneration therapeutics, but their development has been limited by their relatively weakdelivery into target cells. Cationic liposomes have been studied as a means to enhance thestability of nucleic acid therapeutics in the bloodstream and improve their cellular delivery.As nucleic acid therapeutics, siRNA and plasmid DNA have been extensively tested fordelivery using cationic liposomes. This review discusses recent progress in the applicationof cationic liposomes for the delivery of nucleic acid therapeutics.展开更多
Design and synthesis of a carbamate-linked cationic lipid DDCTMA (N-[1-(2,3-didodecylcarbamoyloxy)propyl]-N,N,N-trimethylammonium iodide)? as gene delivery carriers was described in this work. The transfection efficie...Design and synthesis of a carbamate-linked cationic lipid DDCTMA (N-[1-(2,3-didodecylcarbamoyloxy)propyl]-N,N,N-trimethylammonium iodide)? as gene delivery carriers was described in this work. The transfection efficiency of cationic liposome increased dramatically with the increase in the content of DOPE. In addition, the transfection efficiency of some of cationic lipoplexes was superior or parallel to that of two commercial transfection agents, Lipofectamine2000 and DOTAP. The carbamate-linked cationic lipid DDCTMA/DOPE may be a promising gene carrier that has high transfection efficiency as well as low cytotoxicity.展开更多
pH-sensitive liposomes are designed to specifically triggered release the loaded drugs in response to the change of pH in the surrounding serum.So pH-sensitive liposomes can effectively deliver drug or gene fragments ...pH-sensitive liposomes are designed to specifically triggered release the loaded drugs in response to the change of pH in the surrounding serum.So pH-sensitive liposomes can effectively deliver drug or gene fragments into the cytoplasm via the endocytotic pathway.Furthermore,pH-sensitive liposomes can be successfully used in clinical if they enable the encapsulated drugs to be targeted to pathological tissues(such as primary tumors,metastases,local ischemia,inflammation and infection)of the body in which pH is less than the normal physiological value.That’s the reason why a growing amount of literatures described the development and applications of pH-sensitive liposomes to improve the therapeutic index of the encapsulated active ingredients.In this review,the commonly used pH-sensitive molecules for pH-sensitive liposome and the mechanisms of intracellular delivery of pH-sensitive liposomes were addressed.Besides,the potential clinical applications were fully discussed in detail with an expectation to contribute to the clinical research of pH-sensitive liposomes.展开更多
A plasmid DNA vaccine is able to induce both humoral and cellular immune responses;however, the kinetic change of the Th1/Th2 response, antibody avidity, cytokine secretion, and neutralization activity after different...A plasmid DNA vaccine is able to induce both humoral and cellular immune responses;however, the kinetic change of the Th1/Th2 response, antibody avidity, cytokine secretion, and neutralization activity after different priming and boosting strategies have not been evaluated. A plasmid DNA, designated pCBD2 and previously shown to efficiently induce an immune response very similar to that by a wild type virus, was evaluated kinetically in this study. Our results suggest that a DNA vaccine delivered by the gene gun (gg) route produced higher and longer DENV-2-specific antibody titers than those induced through the intramuscular (im) route. Although the gg group induced a Th2 response and im delivery induced a Th1 response, priming by gg delivery, followed by a boosting by im delivery, did not shift the immune response from a Th2 to Th1 response. Furthermore, the antibody avidity (AI) measured by ELISA demonstrated a gradual increase of AI from low (AI range from 6.8% - 9.6%) on day 42 to high (AI value > 30) on day 119 in all but the gene-gun immunization group, in which an AI value of 23 was observed. Although there was lower avidity in the gg group, the mice sera from all three groups of mice demonstrated significant neutralization activity. This is the first report about the kinetics of immunogenicity of a DNA vaccine through different administration strategies, which suggests that gene gun delivery of a DNA vaccine can induce an immune response containing both neutralizing and nonneutralizing antibodies at high titers important for neutralization.展开更多
In this paper, the relatived mechanism between lipofectamine 2000 mediated transmembrane gene delivery and endocytic pathway were investigated. Clathrin and caveolae-mediated endocytic pathway contributions to transfe...In this paper, the relatived mechanism between lipofectamine 2000 mediated transmembrane gene delivery and endocytic pathway were investigated. Clathrin and caveolae-mediated endocytic pathway contributions to transfection efficiency were studied. The inhibitors of endocytosis were used to treat HEp-2 cells before lipofectamine 2000/pGFP-N2 transfection. Transfection efficiency was evaluated with green fluorescence protein (GFP) expression assays. Cell viability and cytotoxicity were evaluated with MTT method. The results indicated that inhibitors of clathrin (chlorpromazine or wortmannin) and caveolin (genistein) could reduce the cell transfection efficiency observably. Both clathrin and caveolae-mediated endocytic pathways play important roles in transmembrane gene delivery.展开更多
基金This work was supported by Research Settlement Fund for the new faculty of Seoul National University,and grants from Ministry of Science,ICT and Future Planning(No.2013035166)from Business for Cooperative R&D between Industry,Academy,and Research Institute funded Korea Small and Medium Business Administration in 2012(No.C0010962).
文摘Nucleic acid-based bioactive substances have recently emerged as a new class of nextgeneration therapeutics, but their development has been limited by their relatively weakdelivery into target cells. Cationic liposomes have been studied as a means to enhance thestability of nucleic acid therapeutics in the bloodstream and improve their cellular delivery.As nucleic acid therapeutics, siRNA and plasmid DNA have been extensively tested fordelivery using cationic liposomes. This review discusses recent progress in the applicationof cationic liposomes for the delivery of nucleic acid therapeutics.
文摘Design and synthesis of a carbamate-linked cationic lipid DDCTMA (N-[1-(2,3-didodecylcarbamoyloxy)propyl]-N,N,N-trimethylammonium iodide)? as gene delivery carriers was described in this work. The transfection efficiency of cationic liposome increased dramatically with the increase in the content of DOPE. In addition, the transfection efficiency of some of cationic lipoplexes was superior or parallel to that of two commercial transfection agents, Lipofectamine2000 and DOTAP. The carbamate-linked cationic lipid DDCTMA/DOPE may be a promising gene carrier that has high transfection efficiency as well as low cytotoxicity.
文摘pH-sensitive liposomes are designed to specifically triggered release the loaded drugs in response to the change of pH in the surrounding serum.So pH-sensitive liposomes can effectively deliver drug or gene fragments into the cytoplasm via the endocytotic pathway.Furthermore,pH-sensitive liposomes can be successfully used in clinical if they enable the encapsulated drugs to be targeted to pathological tissues(such as primary tumors,metastases,local ischemia,inflammation and infection)of the body in which pH is less than the normal physiological value.That’s the reason why a growing amount of literatures described the development and applications of pH-sensitive liposomes to improve the therapeutic index of the encapsulated active ingredients.In this review,the commonly used pH-sensitive molecules for pH-sensitive liposome and the mechanisms of intracellular delivery of pH-sensitive liposomes were addressed.Besides,the potential clinical applications were fully discussed in detail with an expectation to contribute to the clinical research of pH-sensitive liposomes.
文摘A plasmid DNA vaccine is able to induce both humoral and cellular immune responses;however, the kinetic change of the Th1/Th2 response, antibody avidity, cytokine secretion, and neutralization activity after different priming and boosting strategies have not been evaluated. A plasmid DNA, designated pCBD2 and previously shown to efficiently induce an immune response very similar to that by a wild type virus, was evaluated kinetically in this study. Our results suggest that a DNA vaccine delivered by the gene gun (gg) route produced higher and longer DENV-2-specific antibody titers than those induced through the intramuscular (im) route. Although the gg group induced a Th2 response and im delivery induced a Th1 response, priming by gg delivery, followed by a boosting by im delivery, did not shift the immune response from a Th2 to Th1 response. Furthermore, the antibody avidity (AI) measured by ELISA demonstrated a gradual increase of AI from low (AI range from 6.8% - 9.6%) on day 42 to high (AI value > 30) on day 119 in all but the gene-gun immunization group, in which an AI value of 23 was observed. Although there was lower avidity in the gg group, the mice sera from all three groups of mice demonstrated significant neutralization activity. This is the first report about the kinetics of immunogenicity of a DNA vaccine through different administration strategies, which suggests that gene gun delivery of a DNA vaccine can induce an immune response containing both neutralizing and nonneutralizing antibodies at high titers important for neutralization.
文摘In this paper, the relatived mechanism between lipofectamine 2000 mediated transmembrane gene delivery and endocytic pathway were investigated. Clathrin and caveolae-mediated endocytic pathway contributions to transfection efficiency were studied. The inhibitors of endocytosis were used to treat HEp-2 cells before lipofectamine 2000/pGFP-N2 transfection. Transfection efficiency was evaluated with green fluorescence protein (GFP) expression assays. Cell viability and cytotoxicity were evaluated with MTT method. The results indicated that inhibitors of clathrin (chlorpromazine or wortmannin) and caveolin (genistein) could reduce the cell transfection efficiency observably. Both clathrin and caveolae-mediated endocytic pathways play important roles in transmembrane gene delivery.
