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Статті в журналах з теми "Cationic Vector":
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TAN, AMELIA LI MIN, ALISA XUE LING LIM, YITING ZHU, YI YAN YANG, and MAJAD KHAN. "CATIONIC BOLAAMPHIPHILES FOR GENE DELIVERY." COSMOS 10, no. 01 (December 2014): 25–38. http://dx.doi.org/10.1142/s0219607714400059.
Анотація:
Advances in medical research have shed light on the genetic cause of many human diseases. Gene therapy is a promising approach which can be used to deliver therapeutic genes to treat genetic diseases at its most fundamental level. In general, nonviral vectors are preferred due to reduced risk of immune response, but they are also commonly associated with low transfection efficiency and high cytotoxicity. In contrast to viral vectors, nonviral vectors do not have a natural mechanism to overcome extra- and intracellular barriers when delivering the therapeutic gene into cell. Hence, its design has been increasingly complex to meet challenges faced in targeting of, penetration of and expression in a specific host cell in achieving more satisfactory transfection efficiency. Flexibility in design of the vector is desirable, to enable a careful and controlled manipulation of its properties and functions. This can be met by the use of bolaamphiphile, a special class of lipid. Unlike conventional lipids, bolaamphiphiles can form asymmetric complexes with the therapeutic gene. The advantage of having an asymmetric complex lies in the different purposes served by the interior and exterior of the complex. More effective gene encapsulation within the interior of the complex can be achieved without triggering greater aggregation of serum proteins with the exterior, potentially overcoming one of the great hurdles faced by conventional single-head cationic lipids. In this review, we will look into the physiochemical considerations as well as the biological aspects of a bolaamphiphile-based gene delivery system.
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Bengali, Zain, and Lonnie D. Shea. "Gene Delivery by Immobilization to Cell-Adhesive Substrates." MRS Bulletin 30, no. 9 (September 2005): 659–62. http://dx.doi.org/10.1557/mrs2005.193.
Анотація:
AbstractBiomaterials can potentially enhance the delivery of viral and nonviral vectors for both basic science and clinical applications.Vectors typically consist of nucleic acids (DNA, RNA) packaged with proteins, lipids, or cationic polymers, which facilitate cellular internalization and trafficking. These vectors can associate with biomaterials that support cell adhesion, a process we term substrate-mediated delivery. Substrate immobilization localizes the DNA and the delivery vector to the cellular microenvironment.The interaction between the vector and substrate must be appropriately balanced to mediate immobilization, yet allow for cellular internalization. Balancing the binding between the biomaterial and the vector is dependent upon the surface chemistries of the material and the vector, which can be designed to provide both specific (e.g., biotin–avidin, the strongest known noncovalent interaction between a protein and its ligand) and nonspecific (e.g., van der Waals) interactions. In this review, we describe the biomaterial and vector properties that mediate binding and gene transfer, identify potential applications, and present opportunities for further development.
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Nakayama, Yasuhide, Takeshi Masuda, Makoto Nagaishi, Michiko Hayashi, Moto Ohira, and Mariko Harada-Shiba. "High Performance Gene Delivery Polymeric Vector: Nano-Structured Cationic Star Polymers (Star Vectors)." Current Drug Delivery 2, no. 1 (January 1, 2005): 53–57. http://dx.doi.org/10.2174/1567201052772825.
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Porter, Colin D., Katalin V. Lukacs, Gary Box, Yasuhiro Takeuchi, and Mary K. L. Collins. "Cationic Liposomes Enhance the Rate of Transduction by a Recombinant Retroviral Vector In Vitro and In Vivo." Journal of Virology 72, no. 6 (June 1, 1998): 4832–40. http://dx.doi.org/10.1128/jvi.72.6.4832-4840.1998.
Анотація:
ABSTRACT Cationic liposomes enhanced the rate of transduction of target cells with retroviral vectors. The greatest effect was seen with the formulation DC-Chol/DOPE, which gave a 20-fold increase in initial transduction rate. This allowed an efficiency of transduction after brief exposure of target cells to virus plus liposome that could be achieved only after extensive exposure to virus alone. Enhancement with DC-Chol/DOPE was optimal when stable virion-liposome complexes were preformed. The transduction rate for complexed virus, as for virus used alone or with the polycation Polybrene, showed first-order dependence on virus concentration. Cationic liposomes, but not Polybrene, were able to mediate envelope-independent transduction, but optimal efficiency required envelope-receptor interaction. When virus complexed with DC-Chol/DOPE was used to transduce human mesothelioma xenografts, transduction was enhanced four- to fivefold compared to that for virus alone. Since the efficacy of gene therapy is dependent on the number of cells modified, which is in turn dependent upon the balance between transduction and biological clearance of the vector, the ability of cationic liposomes to form stable complexes with retroviral vectors and enhance their rate of infection is likely to be important for in vivo application.
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Guo, Man, Yingcai Meng, Xiaoqun Qin та Wenhu Zhou. "Dopamine-Grafted Hyaluronic Acid Coated Hyperbranched Poly(β-Amino Esters)/DNA Nano-Complexes for Enhanced Gene Delivery and Biosafety". Crystals 11, № 4 (29 березня 2021): 347. http://dx.doi.org/10.3390/cryst11040347.
Анотація:
Gene therapy has attracted particular attention for the treatment of various genetic diseases, and the development of gene delivery vectors is of utmost importance for in vivo applications of gene drugs. Various cationic polymers with high nucleic acid loading and intracellular transfection efficiency have been reported, however, their biological applications are limited by potential toxicity. Surface modification is a robust solution to detoxify the cationic vectors, but this can inevitably weaken the transfection efficiency. To address this dilemma, we reported the ability of a dopamine (DA)-grafted hyaluronic acid (HA) to modify gene vectors for enhanced gene delivery and biosafety. The nano-vector was formed by using branched poly(β-amino esters) (PAEs), and surface coating with HA-DA to form a core-shell nano-structure via electrostatic attraction. Upon HA-DA modification, the biosafety of the gene delivery vehicle was improved, as demonstrated by the cell cytotoxicity assay and hemolysis test. Notably, the nano-system displayed a DA-dependent transfection efficiency, in which a higher DA grafting degree resulted in better efficacy. This can be explained by the adhesive nature of DA, facilitating cell membrane interaction, as well as DA receptor mediated active targeting. At the optimal DA grafting ratio, the nano-system achieved a transfection efficiency even better than that of commonly used polyethylenimine (PEI) vectors. Together with its excellent biocompatibility, the vector presented here holds great promise for gene delivery applications.
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Marquet, Franck, Viorica Patrulea та Gerrit Borchard. "Comparison of triblock copolymeric micelles based on α- and ε-poly(L-lysine): a Cornelian choice". Polymer Journal 54, № 2 (13 жовтня 2021): 199–209. http://dx.doi.org/10.1038/s41428-021-00552-5.
Анотація:
AbstractDue to the lack of safe carriers for the delivery of small interfering RNA (siRNA), clinical applications of nucleotide-based therapeutics have been limited. In this study, biodegradable amphiphilic triblock copolymers with tailored molecular weights for each block composed of methoxy poly(ethylene glycol) (2000 g/mol), poly(L-lysine) (1300 g/mol) and poly(D,L-lactic acid) (1800 g/mol) (mPEG45-α-PLL10-PLA25) were synthesized and fully characterized. The peptide synthesis was carried out on a solid phase to limit the presence of cationic charges. The arrangement and availability of cationic amino groups within a micellar vector were investigated to determine the colloidal stability as well as the predisposition of these systems to vectorize siRNAs in addition to their already known ability to improve the solubility of hydrophobic compounds. For this purpose, a triblock copolymer containing an epsilon poly(L-lysine) was synthesized similarly. Accordingly, the arrangement of the cationic segment modifies the rigidity involving a complexation constraint due to limited cationic charges available on the surface, which can compromise the efficiency of delivery into cells. In addition, the two vectors were biocompatible in different human cell lines.
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Budker, Vladimir, Vladimir Gurevich, James E. Hagstrom, Fedor Bortzov, and Jon A. Wolff. "pH-sensitive, cationic liposomes: A new synthetic virus-like vector." Nature Biotechnology 14, no. 6 (June 1996): 760–64. http://dx.doi.org/10.1038/nbt0696-760.
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Ito, Akira, Tetsuya Takahashi, Yujiro Kameyama, Yoshinori Kawabe, and Masamichi Kamihira. "Magnetic Concentration of a Retroviral Vector Using Magnetite Cationic Liposomes." Tissue Engineering Part C: Methods 15, no. 1 (March 2009): 57–64. http://dx.doi.org/10.1089/ten.tec.2008.0275.
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Natsume, Atsushi, Masaaki Mizuno, Yasushi Ryuke, and Jun Yoshida. "Cationic Liposome Conjugation to Recombinant Adenoviral Vector Reduces Viral Antigenicity." Japanese Journal of Cancer Research 91, no. 4 (April 2000): 363–67. http://dx.doi.org/10.1111/j.1349-7006.2000.tb00953.x.
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El-Mahdy, Ahmed F. M., Takayuki Shibata, Tsutomu Kabashima, Qinchang Zhu, and Masaaki Kai. "Delivery of siRNA using siRNA/cationic vector complexes encapsulated in dendrimer-like polymeric DNAs." RSC Advances 5, no. 41 (2015): 32775–85. http://dx.doi.org/10.1039/c5ra01032b.
Дисертації з теми "Cationic Vector":
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Nouveau, Thibaut. "Nébulisation de nouveaux polyplexes pour le transfert de gènes." Electronic Thesis or Diss., Sorbonne université, 2023. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2023SORUS734.pdf.
Анотація:
La thérapie génique est une forme de thérapie pour traiter les maladies génétiques héréditaires ou acquises tels que les cancers ou la mucoviscidose. L’introduction d’un polynucléotide, par voie systémique ou locale (orale ou nasale par exemple), au sein des cellules malades permet de corriger les défauts à l’origine des mutations génétiques. Néanmoins, le franchissement des différentes barrières biologiques nécessaire à l’internalisation de l’ADN ne peut se faire que par l’intermédiaire d’un vecteur qui va le protéger et lui permettre d’atteindre le noyau de la cellule où il sera transcrit. Divers vecteurs (viraux ou synthétiques) ont vu le jour, tels que des vecteurs polymères cationiques à base de PEI. Cependant, bien qu’efficaces, ces vecteurs sont immunogènes à forte dose. Des fonctionnalisations pour réduire cette toxicité, telle que la PEGylation, ont été mises au point et permettent de renforcer les vecteurs en apportant de la furtivité aux polyplexes finaux. Cependant, ces stratégies montrent des limites nécessitant la synthèse de nouveaux types de polymères. La POxylation représente une bonne alternative à l’utilisation du PEG pour former de nouveaux polyplexes par l’ajout d’un bloc formé d’une ou plusieurs poly(2-alkyl-2-oxazoline)s. Les copolymères sont synthétisés par hydrolyse sélective d’un copolymère triblocs PEtOx-b-PnPrOx-b-PMeOx en utilisant les propriétés thermosensibles des blocs hydrophobes et un sel kosmotrope afin de former des systèmes cœur-couronne permettant l’hydrolyse du bloc PMeOx en PEI. Les systèmes ont ensuite été formulés selon une formulation standard et une méthode par « micro-extrusion ». Les polyplexes ont ensuite été utilisés in vitro par déposition ou par une méthode de nébulisation, idéale pour le traitement de maladies pulmonaires. De très bons résultats de transfection ont été obtenus, résultats qui dépendent de différents paramètres (Mn, PEI, architecture polymère, rapport de charge +/-)Gene therapy is a form of therapy used to treat hereditary or acquired genetic diseases such as cancer or cystic fibrosis. Introducing a polynucleotide into diseased cells, either via the systmeic route or the local route (oral or nasal inhalation), corrects the defects causing the genetic mutations. However, DNA can only be internalized using a vector that protects it and enables it to reach the cell nucleus, where it will be transcribed. Various vectors (viral or synthetic) have been developed, such as PEI-based cationic polymer vectors. However, although effective, these PEI-based vectors are immunogenic at high doses. Functionalizations to reduce this toxicity, such as PEGylation, have been developed, making it possible to reinforce vectors by adding stealthiness to the final polyplexes. However, these strategies have their limitations, necessitating the synthesis of new types of polymer. POxylation represents a good alternative to PEG usage to form new polyplexes by adding a block formed from one or more poly(2-alkyl-2-oxazoline)s. The copolymers are synthesized by selective hydrolysis of a PEtOx-b-PnPrOx-b-PMeOx triblock copolymer using the thermosensitive properties of the hydrophobic blocks and a kosmotropic salt to form core-shell systems enabling hydrolysis of the PMeOx block to PEI. Then, the systems were formulated using a standard formulation and a "micro-extrusion" method. The polyplexes obtained were used in vitro experiments, by deposition or by a nebulization method, ideal for the treatment of pulmonary diseases. Very good transfection results were obtained, depending on various parameters (Mn, PEI, polymer architecture, +/- charge ratio)
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Terp, Megan Cavanaugh. "Improved Nanoparticle Preparation and Delivery Technology for DOTAP and Oligonucleotide Based Lipoplexes." The Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1338301430.
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Ho, J. K. W. "Synthesis and biophysical studies of cationic lipids as gene delivery vectors." Thesis, University College London (University of London), 2012. http://discovery.ucl.ac.uk/1389331/.
Анотація:
Non–viral gene vectors exhibit several desirable properties, over their viral counterparts. This has generated vast interest in the development of efficient non–viral vectors for DNA in gene therapy. The first generation lipid/peptide/DNA (LID) vector was comprised of Lipofectin™, a 1:1 mixture of DOTMA and DOPE, together with a targeting peptide. The resulting LID vector exhibited significant advantages over cationic liposome vectors (lipoplex systems) for gene delivery, transfecting a range of cells with high transfection efficiencies. The LID vector is introduced, and its advantages are outlined. The results and discussion starts in Chapter 2, as we begin our investigation to understand the structural requirements that may lead to enhanced transfection efficiency. The lipid component in the LID vector is described, together with a systematic strategy to enhance transfection activity in the LID vector via new lipid design. The synthesis of a range of C14:1 cationic lipids is described. We have also synthesised asymmetric cationic lipids and lipids containing a short poly(ethylene glycol) (PEG) chain, outlined in Chapter 3. Furthermore, we have synthesised a series of lipids containing a reducible disulfide bridge attached to a PEG moiety, as our strategy is to enhance solubility and shielding during the early stages of cell entry. Once the complex is internalised into the cell, the protective PEG units are shedded, as described in Chapter 4. In addition, the cationic thiol lipid synthesised was coupled to a fluorescent label, to afford a fluorescently–labelled lipid, which has enabled us to track the movement of the lipoplex (lipid:DNA) during transfection. The synthesis towards a cyclic head group for the attachment of different lipid chains is described in Chapter 5. We have utilised a range of synthetic methodologies, including metathesis strategies for the formation of the cyclic lipid precursor. To grasp a greater understanding of how the lipids influence the packaging of DNA, we have studied the biophysical properties of the liposomes and lipoplexes generated at different lipid:DNA mixing ratios, using sizing and zeta potential measurements, given in Chapter 6. The mixing ratios are later used in the design of transfection experiments. Finally, the cationic lipids synthesised in the earlier chapters are formulated into LID complexes, and assessed in a range of different cell lines. The effect of the lipids on transfection efficiency is discussed in Chapter 7. The potential for future work in this area of research is discussed in Chapter 8. A formal description of the experimental procedures and analytical data is presented in Chapter 9.
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Mohammadi, A. "Design and development of tuneable cationic lipopolyplexes as vectors in gene therapy." Thesis, University College London (University of London), 2013. http://discovery.ucl.ac.uk/1389064/.
Анотація:
Gene therapy is a promising technique that offers great potential for the treatment of inherited and acquired disorders. However, one of the major obstacles is identifying suitable vectors with high targeting and transfection efficiency. A literature review on gene therapy and studies on the developments of vectors in gene therapy is presented in Chapter 1. The results and discussion for the development of novel targeting peptides is outlined in Chapter 2. Biophysical analyses of the peptides were performed in PD (peptide-DNA) and LPD (lipid-peptide-DNA) formulations, and found to be stable over time. The protection and release of DNA within the PD and LPD complexes was studied by using gel assays. The DNA binding affinity and transfection efficiencies are presented and discussed. Chapter 3 outlines the synthetic procedures to generate novel glycerol-based cationic lipids. The cationic headgroup was shielded with n-(ethylene glycol) (nEG) chains attached through non degradable and biodegradable linkers. It was noted that the transfection efficiency of formulations of lipid-nEG conjugate with DOPE was increasing with time. Further investigations using mass spectroscopy indicated the transacylation of an oleoyl group from DOPE to the terminal hydroxyl group of lipid-nEG conjugate, resulting in the formation of a new product compromised of three acyl chains (tri-chain lipids). This finding led to the synthesis of several series of novel tri-chain lipids. It was noted that most tri-chained analogues offered an enhanced transfection efficiency and DNA packaging compared to their original di-chained analogues. The synthetic routes towards the formation of novel glycerol-based lipids bearing a disulfide linker are given in Chapter 4. An overall summary and possible areas of future research are discussed in Chapter 5. A formal description of the experimental methods and procedures is presented in Chapter 6.
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Belmadi, Nawal. "Développement, formulation et biodistribution de vecteurs synthétiques pour le transfert de gènes dans le cadre de la thérapie génique de la mucoviscidose." Thesis, Brest, 2015. http://www.theses.fr/2015BRES0093/document.
Анотація:
La mucoviscidose est une maladie monogénique, caractérisée par des mutations survenant au niveau du gène CFTR (Cystic Fibrosis Transmembrane Conductance Regulator). Le clonage en 1989 du gène CFTR a permis d’envisager de traiter cette maladie par thérapie génique. Cela consiste à transférer à l’aide d’un vecteur, une version normale du gène CFTR dans les cellules atteintes des patients. En raison de la gravité des complications pulmonaires, c’est l’épithélium respiratoire qui constitue aujourd’hui le tissu cible pour le transfert de gènes. Le principe de la thérapie génique est évidemment très séduisant et un certain nombre d’essais cliniques ont d’ores et déjà été réalisés. La thérapie génique nécessite des outils de vectorisation efficaces et compatibles avec une utilisation répétée en clinique.Mon sujet de thèse a porté donc sur le développement, la biodistribution et l’optimisation de vecteurs synthétiques (lipides cationiques) pour le transfert de gènes dans l’épithélium respiratoire. Au cours de mes travaux, nous avons donc pu mettre au point des lipophosphoramidates KLN47 fluorescents utiles pour les études de biodistribution in vivo. Comparés au KLN47 non fluorescent, ces nouveaux composés présentent les mêmes propriétés physicochimiques, à savoir une taille relativement petite et un potentiel zêta positif. Sur lignées cellulaires, nous avons montré que les nouvelles formulations étaient aussi efficaces que le KLN47, et pas ou peu toxiques. Ensuite, sur modèle animal, les profils de biodistribution de lipoplexes pégylés et non-pégylés ont été comparés après injection systémique. Les profils de biodistribution des lipoplexes pégylés et non-pégylés étaient similaires, cependant, la pégylation des complexes a conduit à une circulation prolongée dans la circulation sanguine, alors que l’expression du transgène (luciférase) était équivalente dans les deux cas. De plus, l’activité luciférase était similaire à celle obtenue avec le KLN47 non fluorescent. Nous avons ainsi démontré que l’ajout des sondes lipidiques fluorescentes dans la solution liposomale du KLN47, ne modifie pas ses propriétés physicochimiques et transfectantes. L’ensemble des résultats montre que nous disposons d’outils prometteurs pour les études de biodistribution in vivo. D’autres molécules ont également été testées avec succèsCystic fibrosis is a monogenic disease characterized by mutations occurring at the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene. The clonining in 1989 of the CFTR gene has enabled to consider treating this disease by gene therapy. This consists of transferring a normal version of the CFTR gene in the affected patients’ cells, using a vector. Due to the severity of pulmonary complications, it is obvious that the respiratory epithelium constitutes the target tissue for the gene transfer. The principle of gene therapy is indeed very attractive and a number of clinical trials have already been made. Gene therapy requires vectorization tools that are efficient and compatible with repeated clinical use.My thesis has focused on the development, biodistribution and optimization of synthetic vectors (cationic lipids) for gene transfer in the respiratory epithelium. During my work, we were able to develop useful fluorescent KLN47 lipophosphoramidates for in vivo biodistribution studies. Compared to non fluorescent KLN47, these new compounds exhibit the same physicochemical properties: a relatively small size and a positive zeta potential. On cell lines, we found that the new formulations were as effective as the KLN47, with little or no toxicity. Then, in animal models, the biodistribution profiles of pegylated and non-pegylated lipoplexes were compared after systemic injection. The biodistribution profiles of pegylated and non-pegylated lipoplexes were similar. However, the pegylation of the complex resulted in prolonged circulation in the bloodstream, whereas transgene expression (luciferase) was equivalent in both cases. In addition, luciferase activity was similar to that obtained with the non-fluorescent KLN47. We have demonstrated that the addition of fluorescent lipid probes in the liposomal solution KLN47, does not change its physicochemical and transfectant properties. The overall results show that we have promising tools for in vivo biodistribution studies. Other molecules have also been tested successfully
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Cruz, Claudemir Mota da. "Estudo dos campos vetoriais polinomiais quadráticos que possuem integral primeira racional de grau 3." Universidade Federal da Paraíba, 2011. http://tede.biblioteca.ufpb.br:8080/handle/tede/7354.
Анотація:
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This work was dedicated to classify all the global phase portraits of the quadratic polynomial vector fields having a rational first integral of degree three. For this, techniques were used as blow-up, classification of singular points, invariant curves for a system of ordinary diferential equations and vector fields induced on the sphere.
Este trabalho foi dedicado a determinação global dos retratos de fase, no disco de Poincaré, dos campos vetoriais polinomiais quadráticos que possuem integral primeira racional de grau três. Para determinar o retrato de fase, utilizamos técnicas como blow-up, classi- ficação dos pontos singulares, curvas invariantes para um sistema de equações diferenciais ordinárias e a indução de campos vetoriais sobre a esfera.
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Ver?ssimo, Lourena Mafra. "Desenvolvimento de nanosistemas farmac?uticos para terapia g?nica." Universidade Federal do Rio Grande do Norte, 2011. http://repositorio.ufrn.br:8080/jspui/handle/123456789/12638.
Анотація:
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Previous issue date: 2011-03-14Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior
Gene therapy is one of the major challenges of the post-genomic research and it is based on the transfer of genetic material into a cell, tissue or organ in order to cure or improve the patient s clinical status. In general, gene therapy consists in the insertion of functional genes aiming substitute, complement or inhibit defective genes. The achievement of a foreigner DNA expression into a population of cells requires its transfer to the target. Therefore, a key issue is to create systems, vectors, able to transfer and protect the DNA until it reaches the target. The disadvantages related to the use of viral vectors have encouraged efforts to develop emulsions as non-viral vectors. In fact, they are easy to produce, present suitable stability and enable transfection. The aim of this work was to evaluate two different non-viral vectors, cationic liposomes and nanoemulsions, and the possibility of their use in gene therapy. For the two systems, cationic lipids and helper lipids were used. Nanoemulsions were prepared using sonication method and were composed of Captex? 355; Tween? 80; Spam? 80; cationic lipid, Stearylamine (SA) or 1,2-dioleoyl-3-trimethylammoniumpropane (DOTAP) and water (Milli-Q?). These systems were characterized by average droplet size, Polidispersion Index (PI) and Zeta Potential. The stability of the systems; as well as the DNA compaction capacity; their cytotoxicity and the cytotoxicity of the isolated components; and their transfection capacity; were also evaluated. Liposomes were made by hydration film method and were composed of DOTAP; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), containing or not Rhodaminephosphatidylethanolamine (PE- Rhodamine) and the conjugate Hyaluronic Acid DOPE (HA-DOPE). These systems were also characterized as nanoemulsions. Stability of the systems and the influence of time, size of plasmid and presence or absence of endotoxin in the formation of lipoplexes were also analyzed. Besides, the ophthalmic biodistribution of PE-Rhodamine containing liposomes was studied after intravitreal injection. The obtained results show that these systems are promising non-viral vector for further utilization in gene therapy and that this field seems to be very important in the clinical practice in this century. However, from the possibility to the practice, there is still a long way
A terapia g?nica ? um dos maiores desafios propostos pela pesquisa p?s-gen?mica e se baseia na transfer?ncia de material gen?tico a uma c?lula, tecido ou ?rg?o com o intuito de curar ou melhorar o estado cl?nico do paciente. Em sua forma mais simples, a terapia g?nica consiste na inser??o de genes funcionais em c?lulas com genes defeituosos objetivando substituir, complementar ou inibir esses genes causadores de doen?as. Para que o DNA ex?geno seja expresso em uma popula??o celular faz-se necess?ria a sua transfer?ncia at? o local de a??o. Assim, ? necess?rio criar ve?culos, que transportem e protejam o DNA at? que este chegue a uma popula??o celular alvo. Os obst?culos encontrados com a utiliza??o de vetores virais t?m proporcionado o interesse no desenvolvimento de vetores n?o-virais, por serem f?ceis de produzir, apresentarem estabilidade control?vel e facilitarem a transfec??o g?nica. O objetivo deste trabalho foi avaliar dois diferentes vetores n?o virais, lipossomas e nanoemuls?es cati?nicos, e sua poss?vel utiliza??o na terapia g?nica. Para isso, foram utilizados lip?deos cati?nicos e co-tensoativos na produ??o dos dois sistemas. As nanoemuls?es foram produzidas pelo m?todo de sonica??o e compostas por Captex? 355; Tween? 80; Spam? 80; lip?deo cati?nico, Estearilamina (EA) ou N-[1-(2,3-Dioleoiloxi)propil]-N,N,Ntrimetilamonio metilsulfato (DOTAP); e ?gua ultra-pura (Milli-Q?). Estes sistemas foram caracterizados quanto ao tamanho m?dio de got?cula, ?ndice de polidispers?o (PI) e potencial zeta. Avaliou-se ainda a estabilidade dos sistemas e suas capacidades de compacta??o do material gen?tico. Os lipossomas foram preparados a partir do m?todo de hidrata??o do filme e compostos por DOTAP, Dioleilfosfatidiletanolamina (DOPE), na presen?a ou aus?ncia de Rodaminafosfatidiletanolamina (PE-Rodamina) e do conjugado ?cido Hialur?nico DOPE (HA-DOPE). Estes sistemas foram caracterizados da mesma forma que as nanoemuls?es e tamb?m foram avaliados estabilidade, influ?ncia do tempo, tamanho de material gen?tico e presen?a ou aus?ncia de endotoxinas na forma??o dos lipoplexos. Os resultados obtidos permitem afirmar que os sistemas s?o promissores para posterior utiliza??o na terapia g?nica e que esta ?rea promete ser uma ?rea f?rtil de pesquisa cient?fica e cl?nica por muitos anos, e provavelmente se tornar? uma pr?tica cl?nica importante neste s?culo. No entanto, da possibilidade ? pr?tica existe um longo caminho a percorrer
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Le, Bihan Olivier. "Etude par microscopie électronique des mécanismes d'action de vecteurs synthétiques pour le transfert de gènes." Thesis, Bordeaux 1, 2009. http://www.theses.fr/2009BOR13972/document.
Анотація:
La grande majorité des essais cliniques de transfert de gènes in vivo utilise des vecteurs viraux. Si ces derniers sont efficaces, ils présentent des risques immunogènes, toxiques, voire mutagènes avérés. Les vecteurs synthétiques (non viraux), par leur grande modularité et leur faible toxicité représentent une alternative très prometteuse. Le principal frein à leur utilisation est leur manque d’efficacité. L’objectif majeur de ce travail de thèse a été de comprendre le mécanisme de transfert de gènes associé à différents complexes vecteurs synthétiques/ADN plasmidique, ce qui est indispensable pour une conception rationnelle de nouveaux vecteurs. Nous avons étudié, sur cellules en culture, le mécanisme de transfert de gènes associé à deux lipides cationiques ; le BGTC (bis(guanidinium)-tren-cholesterol) et la DOSP (DiOleylamine A-Succinyl-Paromomycine) qui sont connus pour être des vecteurs efficaces in vitro. Nous avons ainsi pu visualiser par microscopie électronique leurs voies d’entrée, leurs remaniements structuraux ainsi que leur échappement endosomal qui représente une étape clé du processus de transfert de gènes. L’identification non ambigüe des lipoplexes tout au long de leur trafic intracellulaire a été rendue possible grâce au marquage de l’ADN par des nanoparticules de silice dotées d’un cœur de maghémite (Fe2O3) dense aux électrons. Cette stratégie de marquage a également été appliquée à l’étude du mécanisme d’action d’un autre vecteur synthétique de type polymère, le copolymère à blocs non ionique P188 ou Lutrol. Contrairement à la plupart des vecteurs synthétiques, celui-ci présente une efficacité de transfection in vivo chez la souris par injection in situ pour le tissu musculaire ou en intra trachéale dans le poumon. En revanche, il est totalement inefficace in vitro. Nous avons montré que le Lutrol permet une augmentation de l’internalisation d’ADN par les cellules mais n’induit pas son échappement endosomal, ce qui expliquerait son absence d’efficacité in vitro. D’autres voies d’entrée sont alors à envisager in vivo pour comprendre son mécanisme d’actionThe vast majority of clinical trials of gene transfer in vivo use viral vectors. Although they are effective, they induce immunogenic, toxic or mutagenic risks. Due to their high modularity and low toxicity, synthetic vectors (non viral), represent a promising alternative despite their lack of effectiveness. The major objective of this work was to understand the mechanism of gene transfer using two prototypic synthetic vectors, in the context of a rational design of new vectors. We studied on cultured cells, the mechanism of action of two cationic lipids; BGTC (bis(guanidinium)-tren-cholesterol) and DOSP (DiOleylamine A-Succinyl-Paromomycine) formulated with plasmid DNA (lipoplexes) which are in vitro efficient vectors. We have been able to visualize by electron microscopy, their intracellular pathways, their structural alterations and their endosomal escape, the latter being a key step in the process of gene transfer. The unambiguous identification of lipoplexes throughout their intracellular trafficking has been made possible thanks to the labelling of DNA by core-shell silica nanoparticles with an electron dense maghemite core (Fe2O3). The labeling strategy has also been applied to study the mechanism of action of a nonionic block copolymer (P188 or Lutrol). Interestingly, these synthetic vectors have an in vivo transfection efficiency in mice lung and muscle tissue while they are totally inefficient in vitro. We have shown that Lutrol induces an increase of DNA internalization into cells and fails to trigger endosomal escape, which would explain the lack of in vitro efficacy. These findings suggest that the in vivo mechanism of action of Lutrol would involve other internalization pathways
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Feng, Tzu-Hua, and 馮子驊. "Synthesis and Characterization of Star-Shaped Cationic Copolymer Hybrid Micelles as a Gene Vector." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/52853289244065649927.
Анотація:
碩士高雄醫學大學
醫藥暨應用化學研究所
100
In this study, amphiphilic star-shaped cationic copolymers were synthesized of hydrophobic monomer and hydrophilic cationic monomer. The synthesized polymer was determined by 1H-NMR spectroscopy and gel permeation chromatography (GPC). The synthesized star-shaped cationic copolymer micelles and hybrid micelles contained PEG are formed by oil-in-water solvent evaporation method. The polyplex binding ability, transfection efficiency and cytotoxicity of micelles are all compared by gel electrophoresis performance, luciferase assay and MTT assay.
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Lee, Chien Hsing, and 李建興. "THE STUDY OF POLYCATIONS AND CATIONIC LIPOSOMES AS A NON-VIRAL VECTOR FOR GENE DELIVERY." Thesis, 2003. http://ndltd.ncl.edu.tw/handle/67776008321623946734.
Анотація:
博士國立臺灣大學
生物化學暨分子生物學研究所
91
During the past years, non-viral gene delivery vector was emerging as a new modality as well as a technology in laboratory and in medical practice. A promising area of research is the design of targeted lipid-DNA complexes. It is clear that the physicochemical properties of lipid-DNA complexes are very important in the design of the ideal lipidic vector. The requirements for such an ideal vector can be summarized as follows: (1) the particles should be small enough to be taken up by organs and surface protected by polyethylene glycol (PEG), to avoid protein interaction in the serum and thus extend their circulation life time into the blood; (2) furthermore, the addition of a targeting ligand is necessary to allow specific recognition by target cells, and (3) the DNA should be condensed and protected from nuclease degradation; (4) finally, DNA should be sufficiently inert to the immune cells to avoid a high level of cytokine production. The results in this report demonstrate the feasibility of improvement in target-specific gene delivery to HER-2-overexpressing cells by insertion of lipid-modified anti-HER-2-Fab’ into the preformed liposomes; in another hand, the large polyethylenimine (PEI) could synergistically increase the transfection efficiency when combined with the cationic liposomes.
Частини книг з теми "Cationic Vector":
1
Jubeli, Emile, William P. D. Goldring, and Michael D. Pungente. "Cationic Lipid-Based Nucleic Acid Vectors." In Methods in Molecular Biology, 19–32. New York, NY: Springer New York, 2016. http://dx.doi.org/10.1007/978-1-4939-3718-9_2.
2
Sherly, M. Caroline Diana, S. S. Priya, and M. R. Rekha. "Cationic Polyelectrolyte Vectors in Gene Delivery." In Particulate Technology for Delivery of Therapeutics, 395–417. Singapore: Springer Singapore, 2017. http://dx.doi.org/10.1007/978-981-10-3647-7_12.
3
Falsini, Sara, and Sandra Ristori. "Lipoplexes from Non-viral Cationic Vectors: DOTAP-DOPE Liposomes and Gemini Micelles." In Methods in Molecular Biology, 33–43. New York, NY: Springer New York, 2016. http://dx.doi.org/10.1007/978-1-4939-3718-9_3.
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Flechsler, Insa, A. Surovoy, K. Charissé, E. Bayer, and G. Jung. "Comparison of Antisense Vectors and Antisense Oligonucleotides Delivered by Means of the New Cationic Lipids Unifectin and Maxifectin." In Advances in Experimental Medicine and Biology, 469–72. Boston, MA: Springer US, 1998. http://dx.doi.org/10.1007/978-1-4615-5357-1_72.
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Arruda, Danielle Campiol, Anne Schlegel, Pascal Bigey, and Virginie Escriou. "Lipoplexes Strengthened by Anionic Polymers: Easy Preparation of Highly Effective siRNA Vectors Based on Cationic Lipids and Anionic Polymers." In Methods in Molecular Biology, 137–48. New York, NY: Springer New York, 2016. http://dx.doi.org/10.1007/978-1-4939-3718-9_8.
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Zahid, Maliha, Xiaoli Lu, Zhibao Mi, and Paul D. Robbins. "Cationic and Tissue-Specific Protein Transduction Domains." In Tissue-Specific Vascular Endothelial Signals and Vector Targeting, Part B, 83–95. Elsevier, 2010. http://dx.doi.org/10.1016/s0065-2660(10)69007-4.
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Bulbake, Upendra, Anjali Jain, and Wahid Khan. "Nanocarriers as Non-Viral Vectors in Gene Delivery Application." In Multifunctional Nanocarriers for Contemporary Healthcare Applications, 357–80. IGI Global, 2018. http://dx.doi.org/10.4018/978-1-5225-4781-5.ch013.
Анотація:
Gene therapy is the emerging trend in biomedical science for treatment of life-threatening diseases. This involves delivery of a therapeutic gene to the nucleus of an affected cell by a suitable vector. Gene delivery using non-viral vectors such as cationic polymer and lipid is gaining attention due to their favourable properties, including lack of immunogenicity, low toxicity, and potential for tissue specificity when compared with viral vectors. A variety of non-viral vectors have been proposed, most of which facilitate gene delivery by electrostatic interactions, encapsulation, and in some cases, condensing nucleic acids into nano-sized particles which can then be taken up by cells. Successful gene delivery within a cell is the nanocarrier's ability to protect its contents from degradation in the extracellular environment. A well-designed nanocarrier will promote cellular uptake and intracellular release of the nucleic acid. This chapter highlights different polymers, lipids, and their nanocarriers employed for gene delivery along with clinical trials.
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"Nomenclature and Classifi cation." In Plant Virus, Vector, 23–30. CRC Press, 2010. http://dx.doi.org/10.1201/9780429196409-6.
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Fang, Yang, and Ke Zhang. "Cationic vs. non-cationic polymeric vectors for nucleic acid delivery." In Reference Module in Materials Science and Materials Engineering. Elsevier, 2021. http://dx.doi.org/10.1016/b978-0-12-822425-0.00024-5.
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Marshall, John, Nelson S. Yew, Simon J. Eastman, Canwen Jiang, Ronald K. Scheule, and Seng H. Cheng. "Cationic Lipid-Mediated Gene Delivery to the Airways." In Nonviral Vectors for Gene Therapy, 39–68. Elsevier, 1999. http://dx.doi.org/10.1016/b978-012358465-6/50015-3.
Тези доповідей конференцій з теми "Cationic Vector":
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Ito, Akira, Tetsuya Takahashi, Yujiro Kameyama, Yoshinori Kawabe, and Masamichi Kamihira. "Magnetic Manipulation of a Retroviral Vector Using Magnetite Cationic Liposomes." In 2008 International Symposium on Micro-NanoMechatronics and Human Science (MHS). IEEE, 2008. http://dx.doi.org/10.1109/mhs.2008.4752479.
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Naruki, M., H. En’yo, R. Muto, T. Tabaru, S. Yokkaichi, Y. Fukao, H. Funahashi, et al. "Medium Modi cation on Vector Mesons Observed in 12 GeV p + A Reactions." In INTERSECTIONS OF PARTICLE AND NUCLEAR PHYSICS: 9th Conference CIPAN2006. AIP, 2006. http://dx.doi.org/10.1063/1.2402687.
Звіти організацій з теми "Cationic Vector":
1
Ohad, Itzhak, and Himadri Pakrasi. Role of Cytochrome B559 in Photoinhibition. United States Department of Agriculture, December 1995. http://dx.doi.org/10.32747/1995.7613031.bard.
Анотація:
The aim of this research project was to obtain information on the role of the cytochrome b559 in the function of Photosystem-II (PSII) with special emphasis on the light induced photo inactivation of PSII and turnover of the photochemical reaction center II protein subunit RCII-D1. The major goals of this project were: 1) Isolation and sequencing of the Chlamydomonas chloroplast psbE and psbF genes encoding the cytochrome b559 a and b subunits respectively; 2) Generation of site directed mutants and testing the effect of such mutation on the function of PSII under various light conditions; 3) To obtain further information on the mechanism of the light induced degradation and replacement of the PSII core proteins. This information shall serve as a basis for the understanding of the role of the cytochrome b559 in the process of photoinhibition and recovery of photosynthetic activity as well as during low light induced turnover of the D1 protein. Unlike in other organisms in which the psbE and psbF genes encoding the a and b subunits of cytochrome b559, are part of an operon which also includes the psbL and psbJ genes, in Chlamydomonas these genes are transcribed from different regions of the chloroplast chromosome. The charge distribution of the derived amino-acid sequences of psbE and psbF gene products differs from that of the corresponding genes in other organisms as far as the rule of "positive charge in" is concerned relative to the process of the polypeptide insertion in the thylakoid membrane. However, the sum of the charges of both subunits corresponds to the above rule possibly indicating co-insertion of both subunits in the process of cytochrome b559 assembly. A plasmid designed for the introduction of site-specific mutations into the psbF gene of C. reinhardtii. was constructed. The vector consists of a DNA fragment from the chromosome of C. reinhardtii which spans the region of the psbF gene, upstream of which the spectinomycin-resistance-conferring aadA cassette was inserted. This vector was successfully used to transform wild type C. reinhardtii cells. The spectinomycin resistant strain thus obtained can grow autotrophically and does not show significant changes as compared to the wild-type strain in PSII activity. The following mutations have been introduced in the psbF gene: H23M; H23Y; W19L and W19. The replacement of H23 involved in the heme binding to M and Y was meant to permit heme binding but eventually alter some or all of the electron transport properties of the mutated cytochrome. Tryptophane W19, a strictly conserved residue, is proximal to the heme and may interact with the tetrapyrole ring. Therefore its replacement may effect the heme properties. A change to tyrosine may have a lesser affect on the potential or electron transfer rate while a replacement of W19 by leucine is meant to introduce a more prominent disturbance in these parameters. Two of the mutants, FW19L and FH23M have segregated already and are homoplasmic. The rest are still grown under selection conditions until complete segregation will be obtained. All mutants contain assembled and functional PSII exhibiting an increased sensitivity of PSII to the light. Work is still in progress for the detailed characterization of the mutants PSII properties. A tobacco mutant, S6, obtained by Maliga and coworkers harboring the F26S mutation in the b subunit was made available to us and was characterized. Measurements of PSII charge separation and recombination, polypeptide content and electron flow indicates that this mutation indeed results in light sensitivity. Presently further work is in progress in the detailed characterization of the properties of all the above mutants. Information was obtained demonstrating that photoinactivation of PSII in vivo initiates a series of progressive changes in the properties of RCII which result in an irreversible modification of the RCII-D1 protein leading to its degradation and replacement. The cleavage process of the modified RCII-D1 protein is regulated by the occupancy of the QB site of RCII by plastoquinone. Newly synthesized D1 protein is not accumulated in a stable form unless integrated in reassembled RCII. Thus the degradation of the irreversibly modified RCII-D1 protein is essential for the recovery process. The light induced degradation of the RCII-D1 protein is rapid in mutants lacking the pD1 processing protease such as in the LF-1 mutant of the unicellular alga Scenedesmus obliquus. In this case the Mn binding site of PSII is abolished, the water oxidation process is inhibited and harmful cation radicals are formed following light induced electron flow in PSII. In such mutants photo-inactivation of PSII is rapid, it is not protected by ligands binding at the QB site and the degradation of the inactivated RCII-D1 occurs rapidly also in the dark. Furthermore the degraded D1 protein can be replaced in the dark in absence of light driven redox controlled reactions. The replacement of the RCII-D1 protein involves the de novo synthesis of the precursor protein, pD1, and its processing at the C-terminus end by an unknown processing protease. In the frame of this work, a gene previously isolated and sequenced by Dr. Pakrasi's group has been identified as encoding the RCII-pD1 C-terminus processing protease in the cyanobacterium Synechocystis sp. PCC 6803. The deduced sequence of the ctpA protein shows significant similarity to the bovine, human and insect interphotoreceptor retinoid-binding proteins. Results obtained using C. reinhardtii cells exposes to low light or series of single turnover light flashes have been also obtained indicating that the process of RCII-D1 protein turnover under non-photoinactivating conditions (low light) may be related to charge recombination in RCII due to back electron flow from the semiquinone QB- to the oxidised S2,3 states of the Mn cluster involved in the water oxidation process.