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https://www.readbyqxmd.com/read/29343574/novel-human-polyomavirus-non-coding-control-regions-differ-in-bi-directional-gene-expression-according-to-host-cell-large-t-antigen-expression-and-clinically-occurring-rearrangements
#1
Elvis T Ajuh, Zongsong Wu, Emma Kraus, Fabian H Weissbach, Tobias Bethge, Rainer Gosert, Nicole Fischer, Hans H Hirsch
Human polyomavirus (HPyV) DNA genomes contain three regions denoted early viral gene region (EVGR) encoding the regulatory T-antigens and one microRNA, late viral gene region (LVGR) encoding the structural Vp capsid proteins, and non-coding control region (NCCR). The NCCR harbours the origin of viral genome replication and bi-directional promoter/enhancer functions governing EVGR- and LVGR-expression on opposite DNA strands. Despite principle similarities, HPyV-NCCRs differ in length, sequence, and architecture...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29336259/p53-as-the-focus-of-gene-therapy-past-present-and-future
#2
Joana Fa Valente, Joao A Queiroz, Fani Sousa
BACKGROUND: Several gene deviations can be responsible for triggering oncogenic processes. However, mutations in tumour suppressor genes are usually more associated to malignant diseases, being p53 one of the most affected and studied element. p53 is implicated in a number of known cellular functions, including DNA damage repair, cell cycle arrest in G1/S and G2/M and apoptosis, being an interesting target for cancer treatment. OBJECTIVE: Considering these facts, the development of gene therapy approaches focused on p53 expression and regulation seems to be a promising strategy for cancer therapy...
January 15, 2018: Current Drug Targets
https://www.readbyqxmd.com/read/29311646/generation-of-functional-dopaminergic-neurons-from-reprogramming-fibroblasts-by-nonviral-based-mesoporous-silica-nanoparticles
#3
Jen-Hsuan Chang, Ping-Hsing Tsai, Kai-Yi Wang, Yu-Ting Wei, Shih-Hwa Chiou, Chung-Yuan Mou
Direct-lineage conversion of the somatic cell by reprogramming, in which mature cells were fully converted into a variety of other cell types bypassing an intermediate pluripotent state, is a promising regenerative medicine approach. Due to the risk of tumorigenesis by viral methods, a non-viral carrier for the delivery of reprogramming factors is very desirable. This study utilized the mesoporous silica nanoparticles (MSNs) as a non-viral delivery system for transduction of the three key factors to achieve conversion of mouse fibroblasts (MFs) into functional dopaminergic neuron-like cells (denoted as fDA-neurons)...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29284260/targeted-stimuli-responsive-delivery-of-plasmid-dna-and-mirnas-using-a-facile-self-assembled-supramolecular-nanoparticle-system
#4
Li-Yen Wong, Bingzhao Xia, Ernst Wolvetang, Justin J Cooper-White
Gene therapy is rapidly regaining traction in terms of research activity and investment across the globe, with clear potential to revolutionise medicine and tissue regeneration. Viral vectors remain the most commonly utilised gene delivery vehicles, due to their high efficiency, however, they are acknowledged to have numerous drawbacks, including limited payload capacity, lack of cell-type specificity, and risk of possible mutations in vivo, hence patient safety. Synthetic nanoparticle gene delivery systems can offer substantial advantages over viral vectors...
December 29, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/29261298/how-to-tune-the-gene-delivery-and-biocompatibility-of-poly-2-4-aminobutyl-2-oxazoline-by-self-and-co-assembly
#5
Meike N Leiske, Fabian H Sobotta, Stephanie Hoeppener, Johannes C Brendel, Anja Traeger, Ulrich S Schubert
Despite their promising potential in gene transfection, the toxicity and limited efficiency of cationic polymers as non-viral vectors are major obstacles for their broader application. The large amount of cationic charges, e.g. in poly(ethylene imine) (PEI) is known to be advantageous in terms of their transfection efficiency, but goes hand-in-hand with a high toxicity. Consequently, an efficient shielding of the charges is required to minimize toxic effects. In this study, we use a simple mixed micelle approach to optimize the required charge density for efficient DNA complex formation and to minimize toxicity by using a biocompatible polymer...
December 20, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/29246287/long-term-pedf-release-in-rat-iris-and-retinal-epithelial-cells-after-sleeping-beauty-transposon-mediated-gene-delivery
#6
Laura Garcia-Garcia, Sergio Recalde, Maria Hernandez, Jaione Bezunartea, Juan Roberto Rodriguez-Madoz, Sandra Johnen, Sabine Diarra, Corinne Marie, Zsuzsanna Izsvák, Zoltán Ivics, Daniel Scherman, Martina Kropp, Gabriele Thumann, Felipe Prosper, Patricia Fernandez-Robredo, Alfredo Garcia-Layana
Pigment epithelium derived factor (PEDF) is a potent antiangiogenic, neurotrophic, and neuroprotective molecule that is the endogenous inhibitor of vascular endothelial growth factor (VEGF) in the retina. An ex vivo gene therapy approach based on transgenic overexpression of PEDF in the eye is assumed to rebalance the angiogenic-antiangiogenic milieu of the retina, resulting in growth regression of choroidal blood vessels, the hallmark of neovascular age-related macular degeneration. Here, we show that rat pigment epithelial cells can be efficiently transfected with the PEDF-expressing non-viral hyperactive Sleeping Beauty transposon system delivered in a form free of antibiotic resistance marker miniplasmids...
December 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/29206023/efficient-gene-delivery-mediated-by-a-helical-polypeptide-controlling-the-membrane-activity-via-multivalency-and-light-assisted-photochemical-internalization-pci
#7
Xin Xu, Yongjuan Li, Qiujun Liang, Ziyuan Song, Fangfang Li, Hua He, Jinhui Wang, Lipeng Zhu, Zhifeng Lin, Lichen Yin
The development of robust and nontoxic membrane-penetrating materials is highly demanded for nonviral gene delivery. Herein, a photosensitizer (PS)-embedded, star-shaped helical polypeptide was developed, which combines the advantages of multivalency-enhanced intracellular DNA uptake and light-strengthened endosomal escape to enable highly efficient gene delivery with low toxicity. 5,10,15,20-Tetrakis-(4-aminophenyl) porphyrin as a selected PS initiated ring-opening polymerization of N-carboxyanhydride and yielded a star-shaped helical polypeptide after side-chain functionalization with guanidine groups...
December 20, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29197187/development-of-a-microfluidic-platform-for-high-throughput-screening-of-non-viral-gene-delivery-vectors
#8
Elisa Giupponi, Roberta Visone, Paola Occhetta, Federica Colombo, Marco Rasponi, Gabriele Candiani
The grail of gene delivery is the development of delivery vectors as effective and non-cytotoxic as possible. In this regard, there is an urgent need of new tools for the straightforward and quantitative assessment of transfection efficiency and cytotoxicity simultaneously. We herein reported the development and validation of an easy-to-use lab-on-chip platform to perform cell transfection assays for unbiased, high-throughput selection of more and more effective gene delivery vectors by using 2 commercially sourced lipids, Lipofectamine 2000® and FuGene® 6...
December 2, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29175597/delivery-of-nf-%C3%AE%C2%BAb-shrna-using-carbamate-mannose-modified-pei-for-eliminating-cancer-stem-cells
#9
Xiyu Ke, Chuan Yang, Wei Cheng, Yi Yan Yang
The presence of cancer stem cells (CSCs) is one of the main reasons that cause cancer relapse and metastasis. In this study, NF-κB shRNA was delivered to target CSCs using carbamate-mannose modified PEI (CMP) as a non-viral gene vector. The polymer was synthesized by blocking primary amine groups of branched PEI (10kDa) through nucleophilic addition between PEI and protected mannose-functionalized cyclic carbonate, followed by mannose deprotection. CMP/control shRNA nanocomplexes showed lower cytotoxicity and higher transfection efficiency in 4 T1 murine breast cancer cells than unmodified PEI/control shRNA nanocomplexes...
November 22, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29175439/lipid-coated-chitosan-dna-nanoparticles-for-enhanced-gene-delivery
#10
Elias Baghdan, Shashank Reddy Pinnapireddy, Boris Strehlow, Konrad H Engelhardt, Jens Schäfer, Udo Bakowsky
Chitosan as a polycationic non-viral vector for gene delivery has the advantage of being a biocompatible and biodegradable polymer. However, without laborious chemical modifications to its structure, it is of limited use as a gene delivery vehicle due to its low ability to efficiently transfect under physiological conditions. To address this problem, we developed novel liposome encapsulated chitosan nanoparticles; lipochitoplexes (LCPs). Chitosan nanoparticles (CsNPs) were obtained using the ionic gelation technique...
November 22, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29158267/methamphetamine-increases-hiv-infectivity-in-neural-progenitor-cells
#11
Marta Skowronska, Marisa McDonald, Martina Velichkovska, Ana Rachel Leda, Minseon Park, Michal Toborek
HIV-1 infection and methamphetamine (METH) abuse frequently occur simultaneously and may have synergistic pathological effects. Although HIV-positive/active METH users have been shown to have higher HIV viral loads and experience more severe neurological complications than non-users, the direct impact of METH on HIV infection and its link to the development of neurocognitive alternations are still poorly understood. In the present study, we hypothesized that METH impacts HIV infection of neural progenitor cells (NPC) by a mechanism encompassing NFκB/SP1-mediated HIV-LTR activation...
November 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29151352/plasmid-dna-delivery-nanotopography-matters
#12
Hao Song, Meihua Yu, Yao Lu, Zhengying Gu, Yannan Yang, Min Zhang, Jianye Fu, Chengzhong Yu
Plasmid DNA molecules with unique loop structures have widespread bio-applications, in many cases relying heavily on delivery vehicles to introduce them into cells and achieve their functions. Herein, we demonstrate that control over delicate nanotopography of silica nanoparticles as plasmid DNA vectors has significant impact on the transfection efficacy. For silica nanoparticles with rambutan-, raspberry- and flower-like morphologies comprised of spike, hemisphere and bowl type subunit nanotopographies, respectively, the rambutan-like nanoparticles with spiky surfaces demonstrate the highest plasmid DNA binding capability and transfection efficacy of 88%, higher than reported silica based nano-vectors...
November 20, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29145481/amiloride-enhanced-gene-transfection-of-octa-arginine-functionalized-calcium-phosphate-nanoparticles
#13
Juan Ramón Vanegas Sáenz, Taichi Tenkumo, Yuya Kamano, Hiroshi Egusa, Keiichi Sasaki
Nanoparticles represent promising gene delivery systems in biomedicine to facilitate prolonged gene expression with low toxicity compared to viral vectors. Specifically, nanoparticles of calcium phosphate (nCaP), the main inorganic component of human bone, exhibit high biocompatibility and good biodegradability and have been reported to have high affinity for protein or DNA, having thus been used as gene transfer vectors. On the other hand, Octa-arginine (R8), which has a high permeability to cell membrane, has been reported to improve intracellular delivery systems...
2017: PloS One
https://www.readbyqxmd.com/read/29137640/direct-reprogramming-of-mouse-fibroblasts-into-neural-cells-via-porphyra-yezoensis-polysaccharide-based-high-efficient-gene-co-delivery
#14
Qingtong Yu, Jingjing Chen, Wenwen Deng, Xia Cao, Yan Wang, Jie Zhou, Wenqian Xu, Pan Du, Qiang Wang, Jiangnan Yu, Ximing Xu
BACKGROUND: The cell source for transplantation therapy is always a prerequisite question to be solved in clinical applications. Neural cells are considered non-regenerable, which highly restrict their application in the treatment for nerve injury. Therefore, neural trans-differentiation based on gene transfection provides a new solution to this issue. Compared to viral strategy, non-viral gene delivery systems are considered as a more promising way to achieve this aim. This study centers on a novel application of Porphyra yezoensis polysaccharide as a non-viral gene carrier for the neural trans-differentiation of mouse fibroblasts...
November 14, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/29129572/biocompatible-fluorinated-poly-%C3%AE-amino-ester-s-for-safe-and-efficient-gene-therapy
#15
Jia-Hui Gong, Yi Wang, Lei Xing, Peng-Fei Cui, Jian-Bin Qiao, Yu-Jing He, Hu-Lin Jiang
Cationic polymers have been widely used as one of the most promising non-viral vehicles for gene delivery due to their potential safety and ease of large-scale production. Here, we report the design and synthesis of a series of novel biodegradable fluorinated poly(β-amino ester)s (FPBAEs) by simple Michael-addition reaction as safe and efficient gene carrier. The results of transfection efficacy assay demonstrated the optimal FPBAE could mediated much higher GFP expression than the commercial transfection agents, polyethyleneimine (PEI, Mw = 25K) and Lipo 2000, as well as the non-fluorinated poly(β-amino ester)s (PBAE) on both HeLa and HEK-293T cell lines (higher than 70 and 90%, respectively), which was largely attributed to fluorination...
November 10, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29121904/generation-of-murine-macrophage-derived-cell-lines-expressing-porcine-cd163-that-support-porcine-reproductive-and-respiratory-syndrome-virus-infection
#16
Liangliang Li, Chunyan Wu, Gaopeng Hou, Biyun Xue, Sha Xie, Qin Zhao, Yuchen Nan, Gaiping Zhang, En-Min Zhou
BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) exhibits a highly restricted tropism for cells of the monocyte-macrophage lineage, utilizing porcine CD163 (pCD163) as an indispensable cellular receptor for infection. Transfection the gene of pCD163 into several non-permissive cell lines followed by protein expression confers susceptibility to PRRSV. A lack of specialized porcine antibody tools for use with existing porcine-derived primary cells and cell lines has hampered studies of both PRRSV pathogenesis and virus triggering of immune response cascades...
November 9, 2017: BMC Biotechnology
https://www.readbyqxmd.com/read/29119921/design-and-delivery-of-therapeutic-sirnas-application-to-mers-coronavirus
#17
Sayed Sartaj Sohrab, Sherif Aly El-Kafrawy, Zeenat Mirza, Mohammad Amjad Kamal, Esam Ibraheem Azhar
BACKGROUND: The MERS-CoV is a novel human coronavirus causing respiratory syndrome since April 2012. The replication of MERS-CoV is mediated by ORF 1ab and viral gene activity can be modulated by RNAi approach. The inhibition of virus replication has been documented in cell culture against multiple viruses by RNAi approach. Currently, very few siRNA against MERS-CoV have been computationally designed and published. METHODS: In this review, we have discussed the computationally designing and delivery of potential siRNAs...
November 8, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29118380/delivery-of-the-gene-encoding-the-tumor-suppressor-sef-into-prostate-tumors-by-therapeutic-ultrasound-inhibits-both-tumor-angiogenesis-and-growth
#18
Sabrin Mishel, Boris Shneyer, Lina Korsensky, Orit Goldshmidt-Tran, Tom Haber, Marcelle Machluf, Dina Ron
Carcinomas constitute over 80% of all human cancer types with no effective therapy for metastatic disease. Here, we demonstrate, for the first time, the efficacy of therapeutic-ultrasound (TUS) to deliver a human tumor suppressor gene, hSef-b, to prostate tumors in vivo. Sef is downregulated in various human carcinomas, in a manner correlating with tumor aggressiveness. In vitro, hSef-b inhibited proliferation of TRAMP C2 cells and attenuated activation of ERK/MAPK and the master transcription factor NF-κB in response to FGF and IL-1/TNF, respectively...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29118372/human-single-chain-transbodies-that-bound-to-domain-i-of-non-structural-protein-5a-ns5a-of-hepatitis-c-virus
#19
Kittirat Glab-Ampai, Monrat Chulanetra, Aijaz Ahmad Malik, Thanate Juntadech, Jeeraphong Thanongsaksrikul, Potjanee Srimanote, Kanyarat Thueng-In, Nitat Sookrung, Pongsri Tongtawe, Wanpen Chaicumpa
A safe and broadly effective direct acting anti-hepatitis C virus (HCV) agent that can withstand the viral mutation is needed. In this study, human single chain antibody variable fragments (HuscFvs) to conserved non-structural protein-5A (NS5A) of HCV were produced by phage display technology. Recombinant NS5A was used as bait for fishing-out the protein bound-phages from the HuscFv-phage display library. NS5A-bound HuscFvs produced by five phage transfected-E. coli clones were linked molecularly to nonaarginine (R9) for making them cell penetrable (become transbodies)...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29116619/evaluation-of-efficiency-of-modified-polypropylenimine-ppi-with-alkyl-chains-as-non-viral-vectors-used-in-co-delivery-of-doxorubicin-and-trail-plasmid
#20
Mahboubeh Ebrahimian, Sahar Taghavi, Maryam Ghoreishi, Shahrzad Sedghi, Sara Amel Farzad, Mohammad Ramezani, Maryam Hashemi
In this study, co-delivery system was achieved via plasmid encoding TNF related apoptosis inducing ligand (pTRAIL) and doxorubicin (DOX) using carrier based on polypropylenimine (PPI) modified with 10-bromodecanoic acid. Incorporation of alkylcarboxylate chain to PPIs (G4 and G5) could improve transfection efficiency via overcoming the plasma membrane barrier of the cells and decrease cytotoxicity of PPI. Characterization of fabricated NPs revealed that PPI G5 in which 30% of primary amines were substituted by alkyl carboxylate chain (PPI G5-Alkyl 30%) has higher drug loading as compared to the other formulations...
November 7, 2017: AAPS PharmSciTech
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