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https://www.readbyqxmd.com/read/28550810/rigid-aromatic-linking-moiety-in-cationic-lipids-for-enhanced-gene-transfection-efficiency
#1
Bing Wang, Rui-Mo Zhao, Ji Zhang, Yan-Hong Liu, Zheng Huang, Qing-Ying Yu, Xiao-Qi Yu
Although numerous cationic lipids have been developed as non-viral gene vectors, the structure-activity relationship (SAR) of these materials remains unclear and needs further investigation. In this work, a series of lysine-derived cationic lipids containing linkages with different rigidity were designed and synthesized. SAR studies showed that lipids with rigid aromatic linkage could promote the formation of tight liposomes and enhance DNA condensation, which is essential for the gene delivery process. These lipids could give much higher transfection efficiency than those containing more flexible aliphatic linkage in various cell lines...
May 17, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28549971/tpp-dendrimer-nanocarriers-for-sirna-delivery-to-the-pulmonary-epithelium-and-their-dry-powder-and-metered-dose-inhaler-formulations
#2
Elizabeth Bielski, Qian Zhong, Hamad Mirza, Matthew Brown, Ashura Molla, Teresa Carvajal, Sandro R P da Rocha
The regulation of genes utilizing the RNA interference (RNAi) mechanism via the delivery of synthetic siRNA has great potential in the treatment of a variety of lung diseases. However, the delivery of siRNA to the lungs is challenging due to the poor bioavailability siRNA when delivered intraveneously, and difficulty in formulating and maintaining the activity of free siRNA when delivered directly to the lungs using inhalation devices. The use of non-viral vectors such as cationic dendrimers can help enhance the stability of siRNA and its delivery to the cell cytosol...
May 23, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28545044/differentiation-of-spontaneously-contracting-cardiomyocytes-from-non-virally-reprogrammed-human-amniotic-fluid-stem-cells
#3
Aaron J Velasquez-Mao, Christopher J M Tsao, Madeline N Monroe, Xavier Legras, Beatrice Bissig-Choisat, Karl-Dimiter Bissig, Rodrigo Ruano, Jeffrey G Jacot
Congenital heart defects are the most common birth defect. The limiting factor in tissue engineering repair strategies is an autologous source of functional cardiomyocytes. Amniotic fluid contains an ideal cell source for prenatal harvest and use in correction of congenital heart defects. This study aims to investigate the potential of amniotic fluid-derived stem cells (AFSC) to undergo non-viral reprogramming into induced pluripotent stem cells (iPSC) followed by growth-factor-free differentiation into functional cardiomyocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28528119/autophagy-plays-a-dual-role-during-intracellular-sirna-delivery-by-lipoplex-and-polyplex-nanoparticles
#4
Wen Song, Zhiwei Ma, Yumei Zhang, Chuanxu Yang
Growing evidence indicates that autophagy plays a vital role during the intracellular DNA delivery mediated by lipoplex and polyplex nanoparticles. However, autophagy in intracellular siRNA delivery has not been well understood. In this study, lipofectamine 2000 and chitosan were used to formulate lipoplex and polyplex with siRNA for systematically investigating the interplay between siRNA delivery and autophagy. After transfection of H1299 cells with lipoplex and polyplex, the number of autophagic vacuoles was increased significantly indicated by the accumulation of monodansylcadaverine (MDC) staining...
May 17, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28513659/serum-resistant-reactive-oxygen-species-ros-potentiated-gene-delivery-in-cancer-cells-mediated-by-fluorinated-diselenide-crosslinked-polyplexes
#5
Qiurong Deng, Xudong Li, Lipeng Zhu, Hua He, Donglai Chen, Yongbing Chen, Lichen Yin
The transfection performance of polycations is often hampered by various systemic barriers that pose conflicting requirements for material design. Herein, we developed fluorinated, ROS-cleavable polyethylenimine (PEI) for effective and serum-resistant gene delivery to cancer cells, by harmonizing the inconsistency between DNA condensation and release, and the inconsistency between cellular internalization and serum stability. Low-molecular weight (MW) PEI was cross-linked with a diselenide-containing linker and further modified with fluorocarbon chains...
May 17, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28511875/visible-light-switched-cytosol-release-of-sirna-by-amphiphilic-fullerene-derivative-to-enhance-rnai-efficacy-in-vitro-and-in-vivo
#6
Jing Wang, Lifei Xie, Tao Wang, Fengxin Wu, Jie Meng, Jian Liu, Haiyan Xu
Cationic macromolecules are attractive for use as small interfering RNA (siRNA) carriers due to their performance in non-immunological reactions, customization during synthesis, and low costs compared to viral carriers. However, their low transfection efficiency substantially hinders their application in both clinical practices and academic research, which is mostly attributable to the low capacity of siRNA/cationic macromolecule complexes to escape lysosomes. To address this challenge, we designed an amphiphilic fullerene derivative (C60-Dex-NH2) for efficient and controllable siRNA delivery...
May 13, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28508949/zn-ii-dipicolylamine-based-metallo-lipids-as-novel-non-viral-gene-vectors
#7
Rong-Chuan Su, Qiang Liu, Wen-Jing Yi, Zhi-Gang Zhao
In this study, a series of Zn(II)-dipicolylamine (Zn-DPA) based cationic lipids bearing different hydrophobic tails (long chains, α-tocopherol, cholesterol or diosgenin) were synthesized. Structure-activity relationship (SAR) of these lipids was studied in detail by investigating the effects of several structural aspects including the type of hydrophobic tails, the chain length and saturation degree. In addition, several assays were used to study their interactions with plasmid DNA, and results reveal that these lipids could condense DNA into nanosized particles with appropriate size and zeta-potentials...
May 16, 2017: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/28508216/rescue-of-sendai-virus-from-cloned-cdna
#8
Shringkhala Bajimaya, Tsuyoshi Hayashi, Toru Takimoto
Sendai virus (SeV) is a non-segment negative-sense RNA virus that naturally infects and causes pneumonia in mice. As a prototypic member of the family Paramyxoviridae, SeV has been characterized well, and these studies revealed numerous traits of paramyxovirus biology. The reverse genetics system to rescue SeV was first established in 1995. The virus was rescued from a cloned cDNA that contains full genome sequence flanked by T7 promoter and hepatitis delta virus ribozyme. To rescue SeV, it is necessary to infect cells with a recombinant vaccinia virus vTF7...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28507462/comparative-analysis-of-non-viral-transfection-methods-in-mouse-embryonic-fibroblast-cells
#9
Migi Lee, Kathleen Chea, Rajyalakshmi Pyda, Melissa Chua, Isabel Dominguez
Mouse embryonic fibroblast (MEF) cells are an important in vitro model for developmental biology, disease, and reprogramming studies. However, as with other primary cells, they are challenging to transfect. Although viral gene-delivery methods achieve high gene-delivery efficiency, challenges with cell mutagenesis and safety among others have led to the use and improvement of non-viral gene-delivery methods in MEF cells. Despite the importance of gene delivery in MEF cells, there is limited comparison of method/reagent efficacy...
April 29, 2017: Journal of Biomolecular Techniques: JBT
https://www.readbyqxmd.com/read/28501672/combining-reactive-triblock-copolymers-with-functional-cross-linkers-a-versatile-pathway-to-disulfide-stabilized-polyplex-libraries-and-their-application-as-pdna-vaccines
#10
Philipp Heller, Dominika Hobernik, Ulrich Lächelt, Meike Schinnerer, Benjamin Weber, Manfred Schmidt, Ernst Wagner, Matthias Bros, Matthias Barz
Therapeutic nucleic acids such as pDNA hold great promise for the treatment of multiple diseases. These therapeutic interventions are, however, compromised by the lack of efficient and safe non-viral delivery systems, which guarantee stability during blood circulation together with high transfection efficiency. To provide these desired properties within one system, we propose the use of reactive triblock copolypept(o)ides, which include a stealth-like block for efficient shielding, a hydrophobic block based on reactive disulfides for cross-linking and a cationic block for complexation of pDNA...
May 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28482577/targeted-delivery-of-bcl-2-conversion-gene-by-mpeg-pcl-pei-fa-cationic-copolymer-to-combat-therapeutic-resistant-cancer
#11
Zibiao Li, Xuan Liu, Xiaohong Chen, Ming Xuan Chua, Yun-Long Wu
Deregulation of anti-apoptosis Bcl-2 protein expression was a key feature in human cancers with therapeutic resistance. Nuclear receptor Nur77 could induce the conformation change of Bcl-2 protein and converted it into an apoptosis inducer by "enemy to friend" strategy. However, the safe and effective delivery of this gene to combat therapeutic resistant cancer remained largely unexplored. In this report, we designed an amphiphilic cationic MPEG-PCL-PEI-FA copolymer, comprising biocompatible and hydrophilic methoxy-poly(ethylene glycol) (MPEG), biodegradable and hydrophobic poly(ε-caprolactone) (PCL), cationic poly(ethylene imine) (PEI) segments, and folic acid (FA) as targeting group, as a high efficient Nur77 gene carrier to folate receptor (FR) highly expressed and therapeutic resistant HeLa/Bcl-2 cancer cells...
July 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28479046/a-triple-fluorophore-labeled-nucleic-acid-ph-nanosensor-to-investigate-non-viral-gene-delivery
#12
David R Wilson, Denis Routkevitch, Yuan Rui, Arman Mosenia, Karl J Wahlin, Alfredo Quinones-Hinojosa, Donald J Zack, Jordan J Green
There is a need for new tools to better quantify intracellular delivery barriers in high-throughput and high-content ways. Here, we synthesized a triple-fluorophore-labeled nucleic acid pH nanosensor for measuring intracellular pH of exogenous DNA at specific time points in a high-throughput manner by flow cytometry following non-viral transfection. By including two pH-sensitive fluorophores and one pH-insensitive fluorophore in the nanosensor, detection of pH was possible over the full physiological range...
May 3, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28476586/manipulating-the-membrane-penetration-mechanism-of-helical-polypeptides-via-aromatic-modification-for-efficient-gene-delivery
#13
Nan Zheng, Ziyuan Song, Jiandong Yang, Yang Liu, Fangfang Li, Jianjun Cheng, Lichen Yin
The delivery performance of non-viral gene vectors is greatly related to their intracellular kinetics. Cationic helical polypeptides with potent membrane penetration properties and gene transfection efficiencies have been recently developed by us. However, they suffer from severe drawbacks in terms of their membrane penetration mechanisms that mainly include endocytosis and pore formation. The endocytosis mechanism leads to endosomal entrapment of gene cargos, while the charge- and helicity-induced pore formation causes appreciable cytotoxicity at high concentrations...
May 2, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28466996/hepatitis-a-virus-cellular-receptor-2-havcr2-is-decreased-with-viral-infection-and-regulates-pro-labour-mediators-oa
#14
Stella Liong, Ratana Lim, Gillian Barker, Martha Lappas
PROBLEM: Intrauterine infection caused by viral infection has been implicated to contribute to preterm birth. Hepatitis A virus cellular receptor 2 (HAVCR2) regulates inflammation in non-gestational tissues in response to viral infection. METHOD OF STUDY: The aims of this study were to determine the effect of: (i) viral dsRNA analogue polyinosinic:polycytidylic acid (poly(I:C)) on HAVCR2 expression; and (ii) HAVCR2 silencing by siRNA (siHAVCR2) in primary amnion and myometrial cells on poly(I:C)-induced inflammation...
May 3, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28466428/extracellular-vesicles-of-etv2-transfected-fibroblasts-stimulate-endothelial-cells-and-improve-neovascularization-in-a-murine-model-of-hindlimb-ischemia
#15
Phuc Van Pham, Ngoc Bich Vu, Thuy Thi-Thanh Dao, Ha Thi-Ngan Le, Lan Thi Phi, Oanh Thuy Huynh, Mai Thi-Hoang Truong, Oanh Thi-Kieu Nguyen, Ngoc Kim Phan
Ischemia are common conditions related to lack of blood supply to tissues. Depending on the ischemic sites, ischemia can cause different diseases, such as hindlimb ischemia, heart infarction and stroke. This study aims to evaluate how extracellular vesicles (EVs) derived from ETV2 transfected fibroblasts affect endothelial cell proliferation and neovascularization in a murine model of hindlimb ischemia. Human fibroblasts were isolated and cultured under standard conditions and expanded to the 3th passage before use in experiments...
May 2, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28453254/gene-transfection-mediated-by-catiomers-requires-free-highly-charged-polymer-chains-to-overcome-intracellular-barriers
#16
Lindomar J C Albuquerque, Carlos E de Castro, Karin A Riske, Maria C Carlan da Silva, Paulo I R Muraro, Vanessa Schmidt, Cristiano Giacomelli, Fernando C Giacomelli
The prospective use of the block copolymers poly(ethylene oxide)113-b-poly[2-(diethylamino)ethyl methacrylate]50 (PEO113-b-PDEA50) and poly[oligo(ethylene glycol)methyl ether methacrylate]70-b-poly[oligo(ethylene glycol)methyl ether methacrylate10-co-2-(diethylamino)ethyl methacrylate47-co-2-(diisopropylamino)ethyl methacrylate47] (POEGMA70-b-P(OEGMA10-co-DEA47-co-DPA47)) as nonviral gene vectors was evaluated. The polymers are able to properly condense DNA into nanosized particles (RH ≈ 75 nm), which are marginally cytotoxic and can be uptaken by cells...
May 5, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28451358/synthetically-controlling-dendrimer-flexibility-improves-delivery-of-large-plasmid-dna
#17
Jessica A Kretzmann, Diwei Ho, Cameron W Evans, Janice H C Plani-Lam, Benjamin Garcia-Bloj, A Elaaf Mohamed, Megan L O'Mara, Ethan Ford, Dennis E K Tan, Ryan Lister, Pilar Blancafort, Marck Norret, K Swaminathan Iyer
Tools for editing the genome and epigenome have revolutionised the field of molecular biology and represent a new frontier in targeted therapeutic intervention. Although efficiencies and specificities of genome editing technologies have improved with the development of TALEs and CRISPR platforms, intracellular delivery of these larger constructs still remains a challenge using existing delivery agents. Viral vectors, including lentiviruses and adeno-associated viruses, as well as some non-viral strategies, such as cationic polymers and liposomes, are limited by packaging capacity, poor delivery, toxicity, and immunogenicity...
April 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28447465/transferrin-dressed-virus-like-ternary-nanoparticles-with-aggregation-induced-emission-for-targeted-delivery-and-rapid-cytosolic-release-of-sirna
#18
Tingbin Zhang, Weisheng Guo, Chunqiu Zhang, Jing Yu, Jing Xu, Shuyi Li, Jian-Hua Tian, Paul C Wang, Jin-Feng Xing, Xing-Jie Liang
Viruses have evolved to be outstandingly efficient at gene delivery, but their use as vectors is limited by safety risks. Inspired by the structure of viruses, we constructed a virus-mimicking vector (denoted as TR4@siRNA@Tf NCs) with virus-like architecture and infection properties. Composed of a hydrophilic peptide, an aggregation-induced emission (AIE) luminogen, and a lipophilic tail, TR4 imitates the viral capsid and endows the vector with AIE properties as well as efficient siRNA compaction. The outer glycoprotein transferrin (Tf) mimics the viral envelope protein and endows the vector with reduced cytotoxicity as well as enhanced targeting capability...
May 3, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28443609/the-hiv-1-viral-synapse-signals-human-foreskin-keratinocytes-to-secrete-thymic-stromal-lymphopoietin-facilitating-hiv-1-foreskin-entry
#19
Z Zhou, L Xu, A Sennepin, C Federici, Y Ganor, D Tudor, D Damotte, N Barry Delongchamps, M Zerbib, M Bomsel
The complexity of signal transduction resulting from the contact of human immunodeficiency virus type 1 (HIV-1)-infected cells and mucosal cells has hampered our comprehension of HIV-1 mucosal entry. Such process is driven efficiently only by viral synapse contacts, whereas cell-free HIV-1 remains poorly infectious. Using CD4(+) T-cells expressing only HIV-1 envelope inoculated on human adult foreskin tissues, we designed methodologies to identify the signals transduced in foreskin keratinocytes following HIV-1-envelope-dependent viral synapse formation...
April 26, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28442771/double-stranded-dna-induces-a-prothrombotic-phenotype-in-the-vascular-endothelium
#20
Erik Gaitzsch, Thomas Czermak, Andrea Ribeiro, Yvonn Heun, Monica Bohmer, Monika Merkle, Hanna Mannell, Christian Schulz, Markus Wörnle, Joachim Pircher
Double-stranded DNA (dsDNA) constitutes a potent activator of innate immunity, given its ability to bind intracellular pattern recognition receptors during viral infections or sterile tissue damage. While effects of dsDNA in immune cells have been extensively studied, dsDNA signalling and its pathophysiological implications in non-immune cells, such as the vascular endothelium, remain poorly understood. The aim of this study was to characterize prothrombotic effects of dsDNA in vascular endothelial cells. Transfection of cultured human endothelial cells with the synthetic dsDNA poly(dA:dT) induced upregulation of the prothrombotic molecules tissue factor and PAI-1, resulting in accelerated blood clotting in vitro, which was partly dependent on RIG-I signalling...
April 25, 2017: Scientific Reports
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