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https://www.readbyqxmd.com/read/29137640/direct-reprogramming-of-mouse-fibroblasts-into-neural-cells-via-porphyra-yezoensis-polysaccharide-based-high-efficient-gene-co-delivery
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
https://www.readbyqxmd.com/read/29093508/vp2-of-chicken-anaemia-virus-interacts-with-apoptin-for-down-regulation-of-apoptosis-through-de-phosphorylated-threonine-108-on-apoptin
#8
Guan-Hua Lai, Yi-Yang Lien, Ming-Kuem Lin, Jai-Hong Cheng, Jason Tc Tzen, Fang-Chun Sun, Meng-Shiunn Lee, Hsi-Jien Chen, Meng-Shiou Lee
Chicken anaemia virus (CAV) is an important contagious agent that causes immunosuppressive disease in chickens. CAV Apoptin is a nucleoplasmic shuffling protein that induces apoptosis in chicken lymphoblastoid cells. In the present study, confocal microscopy revealed co-localisation of expressed CAV non-structural protein VP2 with Apoptin in the nucleus of MDCC-MSB1 cells and the nucleoplasmic compartment of CHO-K1 cells. In vitro pull-down and ex vivo biomolecular fluorescent complementation (BiFC) assays further showed that the VP2 protein directly interacts with Apoptin...
November 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29081256/ternary-complex-of-plasmid-dna-with-nls-mu-mu-protein-and-cationic-niosome-for-biocompatible-and-efficient-gene-delivery-a-comparative-study-with-protamine-and-lipofectamine
#9
Mohammad Hadi Nematollahi, Masoud Torkzadeh-Mahanai, Abbas Pardakhty, Hossein Ali Ebrahimi Meimand, Gholamreza Asadikaram
Non-viral gene delivery methods are considered due to safety and simplicity in human gene therapy. Since the use of cationic peptide and niosome represent a promising approach for gene delivery purposes we used recombinant fusion protein and cationic niosome as a gene carrier. A multi-domain fusion protein including nuclear localization motif (NLS) and two DNA-binding (Mu) domains, namely NLS-Mu-Mu (NMM) has been designed, cloned and expressed in E. coli DE3 strain. Afterward, the interested protein was purified by affinity chromatography...
October 28, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29079806/functionalization-of-microparticles-with-mineral-coatings-enhances-non-viral-transfection-of-primary-human-cells
#10
Andrew S Khalil, Xiaohua Yu, Angela W Xie, Gianluca Fontana, Jennifer M Umhoefer, Hunter J Johnson, Tracy A Hookway, Todd C McDevitt, William L Murphy
Gene delivery to primary human cells is a technology of critical interest to both life science research and therapeutic applications. However, poor efficiencies in gene transfer and undesirable safety profiles remain key limitations in advancing this technology. Here, we describe a materials-based approach whereby application of a bioresorbable mineral coating improves microparticle-based transfection of plasmid DNA lipoplexes in several primary human cell types. In the presence of these mineral-coated microparticles (MCMs), we observed up to 4-fold increases in transfection efficiency with simultaneous reductions in cytotoxicity...
October 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29078136/bioengineering-a-non-genotoxic-vector-for-genetic-modification-of-mesenchymal-stem-cells
#11
Xuguang Chen, Alireza Nomani, Niket Patel, Faranak S Nouri, Arash Hatefi
Vectors used for stem cell transfection must be non-genotoxic, in addition to possessing high efficiency, because they could potentially transform normal stem cells into cancer-initiating cells. The objective of this research was to bioengineer an efficient vector that can be used for genetic modification of stem cells without any negative somatic or genetic impact. Two types of multifunctional vectors, namely targeted and non-targeted were genetically engineered and purified from E. coli. The targeted vectors were designed to enter stem cells via overexpressed receptors...
January 2018: Biomaterials
https://www.readbyqxmd.com/read/29071184/nanoliposomes-for-safe-and-efficient-therapeutic-mrna-delivery-a-step-toward-nanotheranostics-in-inflammatory-and-cardiovascular-diseases-as-well-as-cancer
#12
Meike-Kristin Abraham, Karlheinz Peter, Tatjana Michel, Hans Peter Wendel, Stefanie Krajewski, Xiaowei Wang
Rationale: Genetic therapy using modified mRNA for specific therapeutic protein expression for disease treatment and vaccination represents a new field of therapeutic and diagnostic medicine. Non-viral vectors transfection using biocompatible nanoliposomes enables safe and efficient delivery of therapeutic mRNA. Objective: Generation of non-toxic, cell-compatible cationic nanoliposomes as nanotheranostic agents to successfully deliver therapeutic mRNA. Methods and results: Cationic nanoliposomes (DC-Cholesterol/DOPE) were generated as transfection vehicles for either eGFP mRNA or the therapeutic anti-inflammatory, CD39 mRNA...
2017: Nanotheranostics
https://www.readbyqxmd.com/read/29063914/a-new-developing-class-of-gene-delivery-messenger-rna-based-therapeutics
#13
REVIEW
Zhao Meng, Jonathan O'Keeffe-Ahern, Jing Lyu, Luca Pierucci, Dezhong Zhou, Wenxin Wang
Gene therapy has long been held as having the potential to become a front line treatment for various genetic disorders. However, the direct delivery of nucleic acids to correct a genetic disorder has numerous limitations owing to the inability of naked nucleic acids (DNA and RNA) to traverse the cell membrane. Recently, messenger RNA (mRNA) based delivery has become a more attractive alternative to DNA due to the relatively easier transfection process, higher efficiency and safety profile. As with all gene therapies, the central challenge that remains is the efficient delivery of nucleic acids intracellularly...
October 24, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/29054027/sapofectosid-ensuring-non-toxic-and-effective-dna-and-rna-delivery
#14
Simko Sama, Gerold Jerz, Peter Schmieder, Eric Woith, Matthias F Melzig, Alexander Weng
Different methods are being deployed for non-viral DNA/RNA delivery. However non-viral formulations for DNA/RNA-delivery are often accompanied by severe toxicity and thus low efficiency. Particular costly cell culture media are required as well. Here we introduce sapofection as a valuable enhancing method for non-viral DNA/RNA delivery. Sapofection is based on the application of DNA/RNA nanoplexes and sapofectosid, a plant derived natural transfection reagent. Sapofectosid was produced from plant raw material by chromatographic methods and characterized by tandem mass spectrometry and intensive one and two dimensional NMR-spectroscopy...
October 17, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29050600/evaluation-of-disulfide-bond-conjugated-lmwsc-g-bpei-as-non-viral-vector-for-low-cytotoxicity-and-efficient-gene-delivery
#15
Gyeong-Won Jeong, Jae-Woon Nah
For efficient gene delivery, non-viral vectors should have high cellular uptake, excellent endosomal escape, and the ability to rapidly release the gene into the cytoplasm. Here, we developed a disulfide bond-conjugated bioreducible LMWSC-g-bPEI (LCP) composed of low molecular-weight water soluble chitosan (LMWSC), bPEI, and cystamine (Cys). The developed LCP had advantages such as low toxicity, great endosomal escape, and rapid release of pDNA into the cytoplasm. The polyplexes with LCP showed higher uptake into the nucleus and greater transfection efficiency than that without disulfide bond...
December 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/29046368/enhancement-of-lung-gene-delivery-after-aerosol-a-new-strategy-using-non-viral-complexes-with-antibacterial-properties
#16
Angelique Mottais, Tony Le Gall, Yann Sibiril, Julian Ravel, Véronique Laurent, Frédérique d'Arbonneau, Tristan Montier
The pathophysiology of obstructive pulmonary diseases, such as cystic fibrosis, leads to the development of chronic infections in the respiratory tract. Thus, the symptomatic management of the disease requires, in particular, repetitive antibiotherapy. Besides these antibacterial treatments, certain pathologies, such as cystic fibrosis or chronic obstructive pulmonary disease, require the intake of many drugs. This simultaneous absorption may lead to undesired drug interactions. For example, Orkambi® (lumacaftor/Ivacaftor, Vertex), a pharmacological drug employed to treat F508del patients, cannot be used with antibiotics such as rifampicin or rifabutin (rifamycin family) which are necessary to treat Mycobacteriaceae...
October 18, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29040803/synthesis-and-characterization-of-fatty-acid-grafted-chitosan-polymer-and-their-nanomicelles-for-nonviral-gene-delivery-applications
#17
Divya Sharma, Jagdish Singh
The aim of this study was to synthesize and characterize fatty acid-grafted-chitosan (fatty acid-g-CS) polymer and their nanomicelles for use as carriers for gene delivery. CS was hydrophobically modified using saturated fatty acids of increasing fatty acyl chain length. Carbodiimide along with N-hydroxysuccinimide was used for coupling carboxyl group of fatty acids with amine groups of CS. Proton nuclear magnetic resonance and Fourier transform infrared spectroscopy were used to quantify fatty acyl substitution onto CS backbone...
October 23, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29032724/reintroducing-the-sodium-iodide-symporter-to-anaplastic-thyroid-carcinoma
#18
Kathrin A Schmohl, Patrick Dolp, Christina Schug, Kerstin Knoop, Kathrin Klutz, Nathalie Schwenk, Peter Bartenstein, Peter J Nelson, Manfred Ogris, Ernst Wagner, Christine Spitzweg
BACKGROUND: Anaplastic thyroid carcinoma (ATC), the most aggressive form of thyroid cancer, is unresponsive to radioiodine therapy. The current study aimed to extend the diagnostic and therapeutic application of radioiodine beyond the treatment of differentiated thyroid cancer by targeting the functional sodium-iodide symporter (NIS) to ATC. METHODS: The study employed nanoparticle vectors (polyplexes) based on linear polyethylenimine (LPEI), shielded by polyethylene glycol (PEG) and coupled to the synthetic peptide GE11 as an epidermal growth factor receptor (EGFR)-specific ligand in order to target a NIS-expressing plasmid (LPEI-PEG-GE11/NIS) to EGFR overexpressing human thyroid carcinoma cell lines...
November 10, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/29031805/aptamer-targeted-delivery-of-bcl-xl-shrna-using-alkyl-modified-pamam-dendrimers-into-lung-cancer-cells
#19
Sara Ayatollahi, Zahra Salmasi, Maryam Hashemi, Saeedeh Askarian, Reza Kazemi Oskuee, Khalil Abnous, Mohammad Ramezani
RNAi-based gene therapy has been recently considered as a promising approach against cancer. Targeted delivery of drug, gene or therapeutic RNAi-based systems to tumor cells is one of the important issues in order to reduce side effects on normal cells. Several strategies have been developed to improve the safety and selectivity of cancer treatments including antibodies, peptides and recently aptamers with various attractive characteristics including higher target specificity, affinity and reduced toxicity...
October 12, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29021397/varicella-zoster-virus-expresses-multiple-small-non-coding-rnas
#20
Amos Markus, Linoy Golani, Nishant Kumar Ojha, Tatiana Borodiansky-Shteinberg, Paul R Kinchington, Ronald S Goldstein
Many herpesviruses express small non coding RNAs (sncRNA), including microRNAs (miR), that may play roles in regulating lytic and latent infections. None have yet been reported in varicella zoster virus (VZV, HHV-3). Here we analyzed next generation sequencing (NGS) data for small RNAs in VZV-infected fibroblasts and human embryonic stem cell-derived (hESC) neurons. Two independent bioinformatics analyses identified more than 20 VZV-encoded 20-24 nucleotide RNAs, some of which are predicted to have stem-loop precursors potentially representing miRs...
October 11, 2017: Journal of Virology
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