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https://www.readbyqxmd.com/read/28228595/hepatitis-c-virus-specific-t-cell-receptor-mrna-engineered-human-t-cells-impact-of-antigen-specificity-on-functional-properties
#1
Anangi Balasiddaiah, Haleh Davanian, Soo Aleman, Anna Pasetto, Lars Frelin, Matti Sällberg, Volker Lohmann, Sarene Koh, Antonio Bertoletti, Margaret Chen
Therapy with genetically modified autologous T cells has shown great promise in cancer therapy. For an efficient control of hepatitis C virus (HCV) infection, cytotoxic T cells (CTL) are pivotal but persistence of activated T cells may lead to liver toxicity. Here, anti-HCV T cell receptors (TCRs) recognising the HCV non-structural (NS) NS3 or NS5 viral peptide target were examined by mRNA transfection of human peripheral blood lymphocytes (PBL) derived from healthy donors as well as chronically infected HCV patients...
February 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28227431/bio-active-polymer-implants-to-adipose-tissue-as-in-situ-source-of-reprogramming-cells
#2
Andrey Mikhailov, Fumihiro Sugiyama, Saori Mizuno, Yoshiyuki Sankai, Andrey Mikhailov, Fumihiro Sugiyama, Saori Mizuno, Yoshiyuki Sankai, Saori Mizuno, Andrey Mikhailov, Fumihiro Sugiyama, Yoshiyuki Sankai
The implants from natural polymer chitosan was developed by sorption of non-viral DNA vector. These assemblies were shown to be biocompatible and able to transfect the surrounding cells with reprogramming factors. Transgenic rats from the strain allowing visualization of Nanog-positive stem cells received these implants into their adipose deposits. After 8 days we were able to detect in situ-transfected cells. Transfected cells were positive for YFP fluorescence and transiently expressed the markers correlating with stemness...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28219808/photoluminescent-and-biodegradable-polycitrate-polyethylene-glycol-polyethyleneimine-polymers-as-highly-biocompatible-and-efficient-vectors-for-bioimaging-guided-sirna-and-mirna-delivery
#3
Min Wang, Yi Guo, Meng Yu, Peter X Ma, Cong Mao, Bo Lei
: Development of biodegradable and biocompatible non-viral vectors with intrinsical multifunctional properties such as bioimaging ability for highly efficient nucleic acids delivery still remains a challenge. Here, a biodegradable poly (1, 8-octanedio-citric acid)-co-polyethylene glycol grafted with polyethyleneimine (PEI) (POCG-PEI) polymers with the photoluminescent capacity were synthesized for nucleic acids delivery (siRNA and miRNA). POCG-PEI polymers can efficiently bind various nucleic acids, protect them against enzymatic degradation and release the genes in the presence of polyanionic heparin...
February 17, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28214630/ph-and-reduction-dual-responsive-dipeptide-cationic-lipids-with-%C3%AE-tocopherol-hydrophobic-tail-for-efficient-gene-delivery
#4
Qiang Liu, Rong-Chuan Su, Wen-Jing Yi, Li-Ting Zheng, Shan-Shan Lu, Zhi-Gang Zhao
A series of tocopherol-based cationic lipid 3a-3f bearing a pH-sensitive imidazole moiety in the dipeptide headgroup and a reduction-responsive disulfide linkage were designed and synthesized. Acid-base titration of these lipids showed good buffering capacities. The liposomes formed from 3 and co-lipid 1, 2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) could efficiently bind and condense DNA into nanoparticles. Gel binding and HPLC assays confirmed the encapsulated DNA could release from lipoplexes 3 upon addition of 10 mM glutathione (GSH)...
February 12, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28208635/advances-in-non-viral-dna-vectors-for-gene-therapy
#5
Cinnamon L Hardee, Lirio Milenka Arévalo-Soliz, Benjamin D Hornstein, Lynn Zechiedrich
Uses of viral vectors have thus far eclipsed uses of non-viral vectors for gene therapy delivery in the clinic. Viral vectors, however, have certain issues involving genome integration, the inability to be delivered repeatedly, and possible host rejection. Fortunately, development of non-viral DNA vectors has progressed steadily, especially in plasmid vector length reduction, now allowing these tools to fill in specifically where viral or other non-viral vectors may not be the best options. In this review, we examine the improvements made to non-viral DNA gene therapy vectors, highlight opportunities for their further development, address therapeutic needs for which their use is the logical choice, and discuss their future expansion into the clinic...
February 10, 2017: Genes
https://www.readbyqxmd.com/read/28197596/amphiphilic-polymers-formed-from-ring-opening-polymerization-a-strategy-for-the-enhancement-of-gene-delivery
#6
Yi-Mei Zhang, Zheng Huang, Ji Zhang, Wan-Xia Wu, Yan-Hong Liu, Xiao-Qi Yu
Cationic liposomes and polymers are both important candidates for use as non-viral gene vectors. However, both of them have special shortcomings and application limits. This work is devoted to the combination of advantages of liposomes and polymers. The ring-opening polymerization strategy was used for the preparation of amphiphilic polymers from cyclen-based cationic small lipids. The non-hydrophobic polymer and the corresponding lipids were also prepared for performing structure-activity relationship studies...
February 15, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28196735/gtl001-and-bivalent-cyaa-based-therapeutic-vaccine-strategies-against-human-papillomavirus-and-other-tumor-associated-antigens-induce-effector-and-memory-t-cell-responses-that-inhibit-tumor-growth
#7
Michaël Esquerré, Marie Momot, Anne Goubier, Christophe Gonindard, Stéphane Leung-Theung-Long, Yolande Misseri, Marie-Christine Bissery
GTL001 is a bivalent therapeutic vaccine containing human papillomavirus (HPV) 16 and HPV18 E7 proteins inserted in the Bordetella pertussis adenylate cyclase (CyaA) vector intended to prevent cervical cancer in HPV-infected women with normal cervical cytology or mild abnormalities. To be effective, therapeutic cervical cancer vaccines should induce both a T cell-mediated effector response against HPV-infected cells and a robust CD8(+) T-cell memory response to prevent potential later infection. We examined the ability of GTL001 and related bivalent CyaA-based vaccines to induce, in parallel, effector and memory CD8(+) T-cell responses to both vaccine antigens...
February 10, 2017: Vaccine
https://www.readbyqxmd.com/read/28194746/stimuli-responsive-polymeric-nanocarriers-for-efficient-gene-delivery
#8
REVIEW
Yingqin Li, Jinbiao Gao, Chao Zhang, Zhong Cao, Du Cheng, Jie Liu, Xintao Shuai
Gene therapy provides an alternative and effective method for treatment of genetic diseases and cancers that are refractory to conventional therapeutics. The success of gene therapy is largely dependent on the development of safe and effective gene delivery vectors for transporting genetic material from the blood stream to the cytoplasm or nucleus. Current gene vectors can be divided into viral and non-viral vectors. Although non-viral gene delivery carriers can offer some advantages, such as safety and facile fabrication, they do not possess the same high gene transfection efficiency as viral vectors due to a lack of functionality to overcome extra- and intracellular gene delivery obstacles...
April 2017: Topics in Current Chemistry (Journal)
https://www.readbyqxmd.com/read/28188132/mir-28-regulates-the-germinal-center-reaction-and-blocks-tumor-growth-in-preclinical-models-of-non-hodgkin-lymphoma
#9
Nahikari Bartolomé-Izquierdo, Virginia G de Yébenes, Angel F Álvarez-Prado, Sonia M Mur, Juan A Lopez Del Olmo, Sergio Roa, Jesus Vazquez, Almudena R R Ramiro
Non-Hodgkin Lymphoma (NHL) comprises a variety of neoplasms, many of which arise from germinal center (GC)-experienced B cells. microRNA-28 (miR-28) is a GC-specific microRNA whose expression is lost in numerous mature B cell neoplasms. Here we show that miR-28 regulates the GC reaction in primary B cells by impairing CSR and memory B and plasma cell differentiation. Deep quantitative proteomics combined with transcriptome analysis identified miR-28 targets involved in cell cycle and B cell receptor signaling...
February 10, 2017: Blood
https://www.readbyqxmd.com/read/28185961/non-viral-vectors-based-on-magnetoplexes-lipoplexes-and-polyplexes-for-vegf-gene-delivery-into-central-nervous-system-cells
#10
Ilia Villate-Beitia, Gustavo Puras, Cristina Soto-Sánchez, Mireia Agirre, Edilberto Ojeda, Jon Zarate, Eduardo Fernández, José Luis Pedraz
Nanotechnology based non-viral vectors hold great promise to deliver therapeutic genes into the central nervous system (CNS) in a safe and controlled way. Vascular endothelial growth factor (VEGF) is a potential therapeutic gene candidate for CNS disorders due to its specific roles in brain angiogenesis and neuroprotection. In this work, we elaborated three different non-viral vectors based on magnetic, cationic lipid and polymeric nanoparticles complexed to the phVEGF165aIRESGFP plasmid, which codifies the VEGF protein -extracellular- and the green fluorescent protein (GFP) -intracellular-...
February 6, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28185547/a-novel-scan-statistics-approach-for-clustering-identification-and-comparison-in-binary-genomic-data
#11
Danilo Pellin, Clelia Di Serio
BACKGROUND: In biomedical research a relevant issue is to identify time intervals or portions of a n-dimensional support where a particular event of interest is more likely to occur than expected. Algorithms that require to specify a-priori number/dimension/length of clusters assumed for the data suffer from a high degree of arbitrariness whenever no precise information are available, and this may strongly affect final estimation on parameters. Within this framework, spatial scan-statistics have been proposed in the literature, representing a valid non-parametric alternative...
September 22, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/28179988/ips-derived-mscs-from-an-expandable-bank-to-deliver-a-prodrug-converting-enzyme-that-limits-growth-and-metastases-of-human-breast-cancers
#12
M Ullah, Y Kuroda, T J Bartosh, F Liu, Q Zhao, C Gregory, R Reger, J Xu, R H Lee, D J Prockop
One attractive strategy to treat cancers is to deliver an exogenous enzyme that will convert a non-toxic compound to a highly toxic derivative. The strategy was tested with viral vectors but was disappointing because the efficiency of transduction into tumor cells was too low. Recent reports demonstrated that the limitation can be addressed by using tissue-derived mesenchymal stromal cells (MSCs) to deliver enzyme/prodrug systems that kill adjacent cancer cells through bystander effects. Here we addressed the limitation that tissue-derived MSCs vary in their properties and are difficult to generate in the large numbers needed for clinical applications...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28179536/hiv-aids-vaccine-candidates-based-on-replication-competent-recombinant-poxvirus-nyvac-c-kc-expressing-trimeric-gp140-and-gag-derived-vlps-or-lacking-the-viral-molecule-b19-that-inhibits-type-i-interferon-activate-relevant-hiv-1-specific-b-and-t-cell-immune
#13
Juan García-Arriaza, Beatriz Perdiguero, Jonathan L Heeney, Michael S Seaman, David C Montefiori, Nicole L Yates, Georgia D Tomaras, Guido Ferrari, Kathryn E Foulds, Mario Roederer, Steven G Self, Bhavesh Borate, Raphael Gottardo, Sanjay Phogat, Jim Tartaglia, Susan W Barnett, Brian Burke, Anthony D Cristillo, Deborah E Weiss, Carter Lee, Karen V Kibler, Bertram L Jacobs, Ralf Wagner, Song Ding, Giuseppe Pantaleo, Mariano Esteban
The non-replicating attenuated poxvirus vector NYVAC expressing clade C(CN54) HIV-1 Env(gp120), Gag-Pol-Nef antigens (NYVAC-C) showed in phase I clinical trials limited immunogenicity. To enhance the capacity of the NYVAC vector to trigger broad humoral responses and a more balanced activation of CD4(+) and CD8(+) T cells, here we compared the HIV-1-specific immunogenicity elicited in non-human primates immunized with two replicating NYVAC vectors that have been modified by the insertion of K1L and C7L vaccinia viral host-range genes and express clade C(ZM96) trimeric HIV-1 gp140 protein or a Gag(ZM96)-Pol-Nef(CN54) polyprotein as Gag-derived virus-like particles (termed NYVAC-C-KC)...
February 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28166648/characteristics-of-minimally-oversized-adeno-associated-virus-vectors-encoding-human-factor-viii-generated-using-producer-cell-lines-and-triple-transfection
#14
Bindu Nambiar, Cathleen Cornell Sookdeo, Patricia Berthelette, Robert Jackson, Susan Piraino, Brenda Burnham, Shelley Nass, David Souza, Catherine R O'Riordan, Karen A Vincent, Seng H Cheng, Donna Armentano, Sirkka Kyostio-Moore
Several ongoing clinical studies are evaluating recombinant adeno-associated virus (rAAV) vectors as gene delivery vehicles for a variety of diseases. However, the production of vectors with genomes >4.7 kb is challenging, with vector preparations frequently containing truncated genomes. To determine whether the generation of oversized rAAVs can be improved using a producer cell-line (PCL) process, HeLaS3-cell lines harboring either a 5.1 or 5.4 kb rAAV vector genome encoding codon-optimized cDNA for human B-domain deleted Factor VIII (FVIII) were isolated...
February 2017: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/28165729/harmonizing-the-intracellular-kinetics-toward-effective-gene-delivery-using-cancer-cell-targeted-and-light-degradable-polyplexes
#15
Benchun Jiang, Hua He, Li Yao, Tong Zhang, Jianping Huo, Wei Sun, Lichen Yin
The success of non-viral gene delivery is often restricted by the multiple cellular barriers that posed inconsistent requirements for vector design. High molecular weight (MW) and cationic charge density are required for polycations to enable effective gene encapsulation, which however, also lead to high toxicity, restricted intracellular cargo release, and poor serum resistance. We herein developed crosslinked polyethyleneimine (PEI) with built-in UV-responsive domains (NP-PEI) which can effectively condense DNA while rapidly de-crosslink upon light triggers to promote intracellular DNA release and reduce material toxicity...
February 6, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28152379/selective-transduction-of-astrocytic-and-neuronal-cns-subpopulations-by-lentiviral-vectors-pseudotyped-with-chikungunya-virus-envelope
#16
Ioanna Eleftheriadou, Michael Dieringer, Xuan Ying Poh, Julia Sanchez-Garrido, Yunan Gao, Argyro Sgourou, Laura E Simmons, Nicholas D Mazarakis
Lentiviral vectors are gene delivery vehicles that integrate into the host genome of dividing and non-dividing mammalian cells facilitating long-term transgene expression. Lentiviral vector versatility is greatly increased by incorporating heterologous viral envelope proteins onto the vector particles instead of the native envelope, conferring on these pseudotyped vectors a modified tropism and host range specificity. We investigated the pseudotyping efficiency of HIV-1 based lentiviral vectors with alphaviral envelope proteins from the Chikungunya Virus (CHIKV-G) and Sindbis Virus (SINV-G)...
January 23, 2017: Biomaterials
https://www.readbyqxmd.com/read/28152180/magnetic-nanoparticle-mediated-gene-delivery-to-two-and-three-dimensional-neural-stem-cell-cultures-magnet-assisted-transfection-and-multifection-approaches-to-enhance-outcomes
#17
Mark R Pickard, Christopher F Adams, Divya M Chari
Neural stem cells (NSCs) have high translational potential in transplantation therapies for neural repair. Enhancement of their therapeutic capacity by genetic engineering is an important goal for regenerative neurology. Magnetic nanoparticles (MNPs) are major non-viral vectors for safe bioengineering of NSCs, offering critical translational benefits over viral vectors, including safety, scalability, and ease of use. This unit describes protocols for the production of suspension (neurosphere) and adherent (monolayer) murine NSC cultures...
February 2, 2017: Current Protocols in Stem Cell Biology
https://www.readbyqxmd.com/read/28139696/rewiring-carotenoid-biosynthesis-in-plants-using-a-viral-vector
#18
Eszter Majer, Briardo Llorente, Manuel Rodríguez-Concepción, José-Antonio Daròs
Plants can be engineered to sustainably produce compounds of nutritional, industrial or pharmaceutical relevance. This is, however, a challenging task as extensive regulation of biosynthetic pathways often hampers major metabolic changes. Here we describe the use of a viral vector derived from Tobacco etch virus to express a whole heterologous metabolic pathway that produces the health-promoting carotenoid lycopene in tobacco tissues. The pathway consisted in three enzymes from the soil bacteria Pantoea ananatis...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28137468/the-vector-related-influences-of-autophagic-microrna-delivery-by-lipofectamine-2000-and-polyethylenimine-25k-on-mouse-embryonic-fibroblast-cells
#19
Chia-Wei Lin, Ming-Shiou Jan, Jung-Hua Steven Kuo
Despite the greater potential for clinical applications of autophagic microRNA (miRNA) delivery, the vector-related effects of such delivery on cells have not been fully explored. In this study, autophagic mmu-miR-494-3p (miR-494) in mouse embryonic fibroblast (MEF) cells was selected as a cargo miRNA, and two commonly used non-viral carriers (Lipofectamine 2000 (Lipo) and polyethylenimine 25K (PEI)), were used as delivery vectors to mechanistically elucidate its vector-related effects. The cellular uptake, nuclear localization, and quantitative miR-494 levels of the complexes of miR-494 with Lipo (miR-494 lipoplexes) were lower than those of the complexes of miR-494 with PEI (miR-494 polyplexes) in MEF cells...
January 27, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28134780/viral-vector-mediated-antisense-therapy-for-genetic-diseases
#20
REVIEW
Marine Imbert, Gabriella Dias-Florencio, Aurélie Goyenvalle
RNA plays complex roles in normal health and disease and is becoming an important target for therapeutic intervention; accordingly, therapeutic strategies that modulate RNA function have gained great interest over the past decade. Antisense oligonucleotides (AOs) are perhaps the most promising strategy to modulate RNA expression through a variety of post binding events such as gene silencing through degradative or non-degradative mechanisms, or splicing modulation which has recently demonstrated promising results...
January 26, 2017: Genes
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