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https://www.readbyqxmd.com/read/28103530/an-anti-oxidant-%C3%AE-lipoic-acid-conjugated-oleoyl-sn-phosphatidylcholineas-a-helper-lipid-in-cationic-liposomal-formulations
#1
Priya Dharmalingam, Balakrishna Marrapu, Chandrashekhar Voshavar, Rasagna Nadella, Vignesh Kumar Rangasami, R V Shaji, Salar Abbas, R B N Prasad, Shiva Shanker Kaki, Srujan Marepally
Development of safe non-viral carrier systems for efficient intra-cellular delivery of drugs and genes hold promise in the area of translational research. Liposome based delivery systems have emerged as one of the attractive strategies for efficient delivery of drugs and nucleic acids. To this end, number of investigations was carried on liposomal formulations using lipids for achieving higher efficiency in transfection with lower cytotoxicities. In our efforts to develop safer and efficient liposomal delivery systems, we synthesized a novel anti-oxidant lipid, α-lipoyl, oleyl-sn-phosphatidylcholine (LOPC) and used as a helper lipid in combination with a cationic amphiphile, Di-Stearyl Dihydroxy Ethyl Ammonium Chloride (DSDEAC) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) at varying concentrations of LOPC...
January 10, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28101458/cationic-liposomes-modified-with-polyallylamine-as-a-gene-carrier-preparation-characterization-and-transfection-efficiency-evaluation
#2
Reza Kazemi Oskuee, Asma Mahmoudi, Leila Gholami, Alireza Rahmatkhah, Bizhan Malaekeh-Nikouei
Purpose: Cationic polymers and cationic liposomes have shown to be effective non-viral gene delivery vectors. In this study, we tried to improve the transfection efficiency by employing the advantages of both. Methods: For this purpose, modified polyallylamines (PAAs) were synthesized. These modifications were done through the reaction of PAA (15 KDa) with acrylate and 6-bromoalkanoic acid derivatives. Liposomes comprising of these cationic polymers and cationic lipid were prepared and extruded through polycarbonate filters to obtain desired size...
December 2016: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28100871/in-vivo-direct-reprogramming-of-liver-cells-to-insulin-producing-cells-by-virus-free-overexpression-of-defined-factors
#3
Xiao-Fei Yang, Li-Wei Ren, Lu Yang, Chun-Yan Deng, Fu-Rong Li
Direct reprogramming of autologous cells from diabetes patients to insulin producing cells is a new method for pancreatic cell replacement therapy. At present, transdifferentiation among mature cells is achieved mainly by introducing foreign genes into the starting tissue with viral vector, but there are potentical safety problems. In the present study, we delivered plasmids carrying Pdx1, Neurog3 and MafA genes (PNM) into mouse hepatocytes by hydrodynamics tail vein injection, investigated islet β cells markers in transfected cells from protein and mRNA level, and then observed the long-term control of blood glucose in diabetic mice...
January 18, 2017: Endocrine Journal
https://www.readbyqxmd.com/read/28097097/mir-29a-promotes-lipid-droplet-and-triglyceride-formation-in-hcv-infection-by-inducing-expression-of-srebp-1c-and-cav1
#4
Mennatallah Mamdouh Mahdy, Nada Magdy El-Ekiaby, Rana Mahmoud Hashish, Radwa Ayman Salah, Rasha Sayed Hanafi, Hassan Mohamed El-Said Azzazy, Ahmed Ihab Abdelaziz
Aims: To examine the regulation of SREBP-1c and CAV1 by microRNA-29a (miR-29a) in cells infected with hepatitis C virus (HCV) in an attempt to control HCV-induced non-alcoholic fatty liver disease. Methods: In order to examine the manipulation of SREBP-1c and CAV1 by miR-29a, oleic acid (OA)-treated JFH-I-infected Huh-7 cells were used. OA was added 24 h post-transfection and gene expression was investigated by qRT-PCR at 48 h post treatment. The functional impact of the observed alteration in SREBP-1c and CAV1 expression was analyzed by examining lipid droplet (LD) and triglyceride (TG) content at 72 h post-OA treatment using light microscopy and spectrophotometry, respectively...
December 28, 2016: Journal of Clinical and Translational Hepatology
https://www.readbyqxmd.com/read/28093325/gold-nanostar-polymer-hybrids-for-sirna-delivery-polymer-design-towards-colloidal-stability-and-in-vitro-studies-on-breast-cancer-cells
#5
Carla Sardo, Barbara Bassi, Emanuela F Craparo, Cinzia Scialabba, Elisa Cabrini, Giacomo Dacarro, Agnese D'Agostino, Angelo Taglietti, Gaetano Giammona, Piersandro Pallavicini, Gennara Cavallaro
To overcome the low bioavailability of siRNA (small interfering RNA) and to improve their transfection efficiency, the use of non-viral delivery carriers is today a feasible approach to transform the discovery of these incredibly potent and versatile drugs into clinical practice. Polymer-modified gold nanoconstructs (AuNCs) are currently viewed as efficient and safe intracellular delivery carriers for siRNA, as they have the possibility to conjugate the ability to stably entrap and deliver siRNAs inside cells with the advantages of gold nanoparticles, which can act as theranostic agents and radiotherapy enhancers through laser-induced hyperthermia...
January 13, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28079203/complexation-of-short-ds-rna-dna-oligonucleotides-with-gemini-micelles-a-time-resolved-saxs-and-computational-study
#6
Sara Falsini, Emanuela Di Cola, Martin In, Maria Giordani, Stefano Borocci, Sandra Ristori
Gene therapy is based on nucleic acid delivery to pathogenic cells in order to modulate their gene expression. The most used non viral vectors are lipid-based nanoaggregates, which are safer than viral carriers and have been shown to assemble easily with both DNA and RNA. However, the transfection efficiency of non viral carriers still needs to be improved before intensive practise in clinical trials can be implemented. For this purpose, the in depth characterization of the complexes formed by nucleic acids and their transporters is of great relevance...
January 12, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28074350/a-comparative-study-of-the-bone-regenerative-effect-of-chemically-modified-rna-encoding-bmp-2-or-bmp-9
#7
Behnoush Khorsand, Satheesh Elangovan, Liu Hong, Alexander Dewerth, Michael S D Kormann, Aliasger K Salem
Employing cost-effective biomaterials to deliver chemically modified ribonucleic acid (cmRNA) in a controlled manner addresses the high cost, safety concerns, and lower transfection efficiency that exist with protein and gene therapeutic approaches. By eliminating the need for nuclear entry, cmRNA therapeutics can potentially overcome the lower transfection efficiencies associated with non-viral gene delivery systems. Here, we investigated the osteogenic potential of cmRNA-encoding BMP-9, in comparison to cmRNA-encoding BMP-2...
January 10, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28054985/novel-pei-poly-%C3%AE-gutamic-acid-nanoparticles-for-high-efficient-sirna-and-plasmid-dna-co-delivery
#8
Shu-Fen Peng, Hung-Kun Hsu, Chun-Cheng Lin, Ya-Ming Cheng, Kuang-Hsing Hsu
The efficient delivery of sufficient amounts of nucleic acids into target cells is critical for successful gene therapy and gene knockdown. The DNA/siRNA co-delivery system has been considered a promising approach for cancer therapy to simultaneously express and inhibit tumor suppressor genes and overexpressed oncogenes, respectively, triggering synergistic anti-cancer effects. Polyethylenimine (PEI) has been identified as an efficient non-viral vector for transgene expression. In this study, we created a very high efficient DNA/siRNA co-delivery system by incorporating a negatively-charged poly-γ-glutamic acid (γ-PGA) into PEI/nucleic acid complexes...
January 4, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28042541/rational-development-of-a-polycistronic-plasmid-with-a-cpg-free-bacterial-backbone-as-a-potential-tool-for-direct-reprogramming
#9
Kianoush Dormiani, Hamid Mir Mohammad Sadeghi, Hojjat Sadeghi-Aliabadi, Mahboobeh Forouzanfar, Hossein Baharvand, Kamran Ghaedi, Mohammad Hossein Nasr-Esfahani
OBJECTIVE: Induced pluripotent stem cells are generated from somatic cells by direct reprogramming. These reprogrammed pluripotent cells have different applications in biomedical fields such as regenerative medicine. Although viral vectors are widely used for efficient reprogramming, they have limited applications in the clinic due to the risk for immunogenicity and insertional mutagenesis. Accordingly, we designed and developed a small, non-integrating plasmid named pLENSO/Zeo as a 2A-mediated polycistronic expression vector...
2017: Cell Journal
https://www.readbyqxmd.com/read/28025049/polylysine-modified-polyethylenimine-pei-pll-mediated-vegf-gene-delivery-protects-dopaminergic-neurons-in-cell-culture-and-in-rat-models-of-parkinson-s-disease-pd
#10
Muhammad Abid Sheikh, Yousra Saeed Malik, Zhenkai Xing, Zhaopei Guo, Huayu Tian, Xiaojuan Zhu, Xuesi Chen
Parkinson's Disease (PD) is a chronic neurodegenerative disorder characterized by motor deficits which result from the progressive loss of dopaminergic neurons. Gene therapy using growth factors such as VEGF seems to be a viable approach for potential therapeutic treatment of PD. In this study, we utilized a novel non-viral gene carrier designated as PEI-PLL synthesized by our laboratory to deliver VEGF gene to study its effect by using both cell culture as well as animal models of PD. For cell culture experiments, we utilized 6-hydroxydopamine (6-OHDA) mediated cell death model of MN9D cells following transfection with either a control plasmid or VEGF expressing plasmid...
December 23, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/28017770/efficient-gene-delivery-to-primary-human-retinal-pigment-epithelial-cells-the-innate-and-acquired-properties-of-vectors
#11
Nooshin Tasharrofi, Fatemeh Kouhkan, Masoud Soleimani, Zahra-Soheila Soheili, Fatemeh Atyabi, Hamid Akbari Javar, Farid Abedin Dorkoosh
The purpose of this study is designing non-viral gene delivery vectors for transfection of the primary human retinal pigment epithelial cells (RPE). In the design process of gene delivery vectors, considering physicochemical properties of vectors alone does not seem to be enough since they interact with constituents of the surrounding environment and hence gain new characteristics. Moreover, due to these interactions, their cargo can be released untimely or undergo degradation before reaching to the target cells...
December 23, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28011343/design-and-characterization-of-a-magnetite-pei-multifunctional-nanohybrid-as-non-viral-vector-and-cell-isolation-system
#12
Raúl Megías, Maialen Arco, Jesús Ciriza, Laura Saenz Del Burgo, Gustavo Puras, Margarita López-Viota, Ángel V Delgado, Jon P Dobson, José L Arias, José L Pedraz
It is described the reproducible formulation and complete physicochemical characterization of nanohybrids based on magnetite (Fe3O4) cores embedded within a polyethylenimine (PEI) matrix. Particle size, surface electrical charge, X-ray diffraction and Fourier transform infrared spectroscopy (FTIR) analyses, and magnetic field-responsive behaviour characterizations defined that the 4:3 (Fe3O4:PEI) weight proportion led to the best production performances of magnetically responsive nanocomposites in which the magnetic nuclei are completely covered by the polymeric shell...
December 21, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28005327/construction-of-plga-nanoparticles-coated-with-polycistronic-sox5-sox6-and-sox9-genes-for-chondrogenesis-of-human-mesenchymal-stem-cells
#13
Ji Sun Park, Se Won Yi, Hye Jin Kim, Seong Min Kim, Jae-Hwan Kim, Keun-Hong Park
Transfection of a cocktail of genes into cells has recently attracted attraction in stem cell differentiation. However, it is not easy to control the transfection rate of each gene. To control and regulate gene delivery into human mesenchymal stem cells (hMSCs), we employed multicistronic genes coupled with a nonviral gene carrier system for stem cell differentiation. Three genes, SOX5, SOX6, and SOX9, were successfully fabricated in a single plasmid. This multicistronic plasmid was complexed with the polycationic polymer polyethylenimine, and poly(lactic-co-glycolic) acid (PLGA) nanoparticles were coated with this complex...
January 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27993732/fast-therapeutic-dna-internalization-a-high-potential-transfection-system-based-on-a-peptide-mimicking-cationic-lipid
#14
Christopher Janich, Shashank Reddy Pinnapireddy, Frank Erdmann, Thomas Groth, Andreas Langner, Udo Bakowsky, Christian Wölk
The delivery of nucleic acids into cells is a determining factor for successful gene therapy. In this study we investigate the uptake and time dependent processing of a lipid-based non-viral nucleic acid delivery system composed of a peptide-mimicking cationic lipid (N-{6-amino-1-[N-(9Z)-octadec-9-enylamino]-1-oxohexan-(2S)-2-yl}-N'-{2-[N,N-bis(2-aminoethyl)amino]ethyl}-2-hexadecylpropandiamide - OH4) and a phospholipid (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine - DOPE). Studies by confocal laser scanning microscopy (CLSM) indicate a rapid internalization of fluorescent labelled DNA within 1h...
December 18, 2016: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/27968705/efficient-nonviral-transfection-of-primary-intervertebral-disc-cells-by-electroporation-for-tissue-engineering-application
#15
Rahel D May, Adel Tekari, Daniela A Frauchiger, Anna Krismer, Lorin M Benneker, Benjamin Gantenbein
Low back pain (LBP) is an increasing global health problem associated with intervertebral disc (IVD) trauma and degeneration. Current treatment options include surgical interventions with partial unsatisfactory outcomes reported such as failure to relieve LBP, nonunions, nerve injuries, or adjacent segment disease. Cell-based therapy and tissue engineered IVD constructs supplemented with transfected disc cells that incorporate factors enhancing matrix synthesis represent an appealing approach to regenerate the IVD...
January 2017: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/27940045/transfer-of-the-bone-morphogenetic-protein-4-gene-into-rat-periodontal-ligament-by-in-vivo-electroporation
#16
Shinobu Tsuchiya, Mirei Chiba, Koshi N Kishimoto, Harukazu Nakamura, Masahiro Tsuchiya, Haruhide Hayashi
OBJECTIVE: Regulation of alveolar bone metabolism is required in clinical dentistry. The aim of the present study was to establish a method for gene transfer into the periodontal ligament (PDL) by in vivo electroporation with a plasmid vector and to investigate the effects of BMP-4 transfer into the PDL. DESIGN: Plasmids containing mouse BMP-4 cDNA (pCAGGS-BMP4) were transfected into cultured rat PDL cells by in vitro electroporation, and BMP-4 production and secretion were detected by immunocytochemistry and western blotting...
February 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/27935984/a-biodegradable-polyethylenimine-based-vector-modified-by-trifunctional-peptide-r18-for-enhancing-gene-transfection-efficiency-in-vivo
#17
Jing Hu, Manman Zhu, Kehai Liu, Hua Fan, Wenfang Zhao, Yuan Mao, Yaguang Zhang
Lack of capacity to cross the nucleus membrane seems to be one of the main reasons for the lower transfection efficiency of gene vectors observed in vivo study than in vitro. To solve this problem, a new non-viral gene vector was designed. First, a degradable polyethylenimine (PEI) derivate was synthesized by crosslinking low-molecular-weight (LMW) PEI with N-octyl-N-quaternary chitosan (OTMCS), and then adopting a designed trifunctional peptide (RGDC-TAT-NLS) with good tumor targeting, cell uptake and nucleus transport capabilities to modify OTMCS-PEI...
2016: PloS One
https://www.readbyqxmd.com/read/27924861/size-specific-transfection-to-mammalian-cells-by-micropillar-array-electroporation
#18
Yingbo Zu, Shuyan Huang, Yang Lu, Xuan Liu, Shengnian Wang
Electroporation serves as a promising non-viral gene delivery approach, while its current configuration carries several drawbacks associated with high-voltage electrical pulses and heterogeneous treatment on individual cells. Here we developed a new micropillar array electroporation (MAE) platform to advance the electroporation-based delivery of DNA and RNA probes into mammalian cells. By introducing well-patterned micropillar array texture on the electrode surface, the number of pillars each cell faces varies with its plasma membrane surface area, despite their large population and random locations...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27920474/hepatitis-b-virus-upregulates-host-expression-of-%C3%AE-1-2-mannosidases-via-the-ppar%C3%AE-pathway
#19
Song Hu, Li-Bin Jiang, Xiao-Jing Zou, Wei Yi, De-Ying Tian
AIM: To assess the effects of hepatitis B virus (HBV) on the expression of host α-1,2-mannosidases and determine the underlying mechanisms. METHODS: We measured the expression levels of MAN1A1, MAN1A2, MAN1B1, and MAN1C1 in cell lines HepG2.2.15, HepN10, HepAD38 and HepG2 by Western blot. Viral antigens (HBsAg and HBeAg) in the culture medium were measured using the chemiluminescence method. HBV DNA quantification assays were performed using a commercial real-time PCR kit...
November 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27918590/effects-of-circular-dna-length-on-transfection-efficiency-by-electroporation-into-hela-cells
#20
Benjamin D Hornstein, Dany Roman, Lirio M Arévalo-Soliz, Melinda A Engevik, Lynn Zechiedrich
The ability to produce extremely small and circular supercoiled vectors has opened new territory for improving non-viral gene therapy vectors. In this work, we compared transfection of supercoiled DNA vectors ranging from 383 to 4,548 bp, each encoding shRNA against GFP under control of the H1 promoter. We assessed knockdown of GFP by electroporation into HeLa cells. All of our vectors entered cells in comparable numbers when electroporated with equal moles of DNA. Despite similar cell entry, we found length-dependent differences in how efficiently the vectors knocked down GFP...
2016: PloS One
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