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polymers and gene transfer

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https://www.readbyqxmd.com/read/28716960/bacterial-tubulin-a-b-exhibit-polarized-growth-mixed-polarity-bundling-and-destabilization-by-gtp-hydrolysis
#1
César Díaz-Celis, Viviana I Risca, Felipe Hurtado, Jessica K Polka, Scott D Hansen, Daniel Maturana, Rosalba Lagos, R Dyche Mullins, Octavio Monasterio
Bacteria of the genus Prosthecobacter express homologs of eukaryotic α- and β-tubulin, called BtubA and BtubB, that have been observed to assemble into filaments in presence of GTP. BtubA/B polymers are proposed to be composed in vitro by two to six protofilaments, in contrast to in vivo where they have been reported to form 5-protofilaments tubes named bacterial microtubules (bMTs). The btubAB genes likely entered the Prosthecobacter lineage via horizontal gene transfer and may derive from an early ancestor of the modern eukaryotic microtubule (MT)...
July 17, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28694032/biodegradable-brain-penetrating-dna-nanocomplexes-and-their-use-to-treat-malignant-brain-tumors
#2
Panagiotis Mastorakos, Clark Zhang, Eric Song, Young Eun Kim, Hee Won Park, Sneha Berry, Won Kyu Choi, Justin Hanes, Jung Soo Suk
The discovery of powerful genetic targets has spurred clinical development of gene therapy approaches to treat patients with malignant brain tumors. However, lack of success in the clinic has been attributed to the inability of conventional gene vectors to achieve gene transfer throughout highly disseminated primary brain tumors. Here, we demonstrate ex vivo that small nanocomplexes composed of DNA condensed by a blend of biodegradable polymer, poly(β-amino ester) (PBAE), with PBAE conjugated with 5kDa polyethylene glycol (PEG) molecules (PBAE-PEG) rapidly penetrate healthy brain parenchyma and orthotopic brain tumor tissues in rats...
July 8, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28640589/ru-bpy-3-2-incorporated-luminescent-polymer-dots-double-enhanced-electrochemiluminescence-for-detection-of-single-nucleotide-polymorphism
#3
Yaqiang Feng, Feng Sun, Ningning Wang, Jianping Lei, Huangxian Ju
Encapsulating a large amount of electrochemiluminescence (ECL) active molecules into one nanoparticle for single-target recognition can greatly improve the sensitivity of the ECL assay. This work used luminescent conjugated polymer as a carrier to synthesize Ru(bpy)3(2+)-doped polymer dots (RuPdots). The RuPdots with an average size of 20 nm and encapsulation of about 1354 Ru(bpy)3(2+) showed greatly enhanced ECL emission. Using tripropylamine as a coreactant, the resonance energy transfer from the excited polymer dots to the encapsulated Ru(bpy)3(2+) was demonstrated, which led to a 15...
June 30, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28619643/superior-transfection-efficiency-of-phagocytic-astrocytes-by-large-chitosan-dna-nanoparticles
#4
Fanqiang Kong, Guoping Liu, Shumin Zhou, Jie Guo, Song Chen, Zhiyun Wang
PURPOSE: Mechanism study of why astrocytes isolated from experimental autoimmune encephalomyelitis (EAE)-induced B6 mice or after being exposed to inflammatory factors had the highest transfection efficiency to larger-sized, but not compacted, pspCS/pDNA particles. METHODS: Phosphorylatable short peptide conjugated chitosan (pspCS) was compounded with plasmid DNA (pDNA) at different N:P ratios to form pspCS/pDNA particles of different size and zeta potentials. These pspCS/pDNA particles were used for the transfection of astrocytes isolated from either EAE induced or healthy B6 mice...
June 12, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28567486/xenobiology-state-of-the-art-ethics-and-philosophy-of-new-to-nature-organisms
#5
Markus Schmidt, Lei Pei, Nediljko Budisa
The basic chemical constitution of all living organisms in the context of carbon-based chemistry consists of a limited number of small molecules and polymers. Until the twenty-first century, biology was mainly an analytical science and has now reached a point where it merges with engineering science, paving the way for synthetic biology. One of the objectives of synthetic biology is to try to change the chemical compositions of living cells, that is, to create an artificial biological diversity, which in turn fosters a new sub-field of synthetic biology, xenobiology...
June 1, 2017: Advances in Biochemical Engineering/biotechnology
https://www.readbyqxmd.com/read/28532005/non-viral-strategies-for-ocular-gene-delivery
#6
REVIEW
Ana V Oliveira, Ana M Rosa da Costa, Gabriela A Silva
The success of gene therapy relies on efficient gene transfer and stable transgene expression. The in vivo efficiency is determined by the delivery vector, route of administration, therapeutic gene, and target cells. While some requirements are common to several strategies, others depend on the target disease and transgene product. Consequently, it is unlikely that a single system is suitable for all applications. This review examines current gene therapy strategies, focusing on non-viral approaches and the use of natural polymers with the eye, and particularly the retina, as their gene delivery target...
August 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28510447/synthesis-of-a-highly-azide-reactive-and-thermosensitive-biofunctional-reagent-for-efficient-enrichment-and-large-scale-identification-of-o-glcnac-proteins-by-mass-spectrometry
#7
Wanjun Zhang, Tong Liu, Hangyan Dong, Haihong Bai, Fang Tian, Zhaomei Shi, Mingli Chen, Jianhua Wang, Weijie Qin, Xiaohong Qian
O-linked β-N-acetylglucosamine (O-GlcNAc) is a ubiquitous post-translational modification of proteins in eukaryotic cells. Despite their low abundance, O-GlcNAc-modified proteins play many important roles in regulating gene expression, signal transduction, and cell cycle. Aberrant O-GlcNAc proteins are correlated with many major human diseases, such as Alzheimer's disease, diabetes, and cancer. Because of the extremely low stoichiometry of O-GlcNAc proteins, enrichment is required before mass spectrometry analysis for large-scale identification and in-depth understanding of their cellular function...
June 6, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28483693/combined-delivery-of-a-tgf-%C3%AE-inhibitor-and-an-adenoviral-vector-expressing-interleukin-12-potentiates-cancer-immunotherapy
#8
Jiayu Jiang, Yuandong Zhang, Ke Peng, Qin Wang, Xiaoyu Hong, Hanmei Li, Gerui Fan, Zhirong Zhang, Tao Gong, Xun Sun
Cancer immunotherapy appears a promising future, but it can be thwarted by secretion of immunosuppressive factors, such as transforming growth factor-β (TGF-β), which inhibits local immune responses to tumors. To weaken immune resistance of tumors and simultaneously strengthen immune responses, we developed a multifunctional polymer that could co-deliver hydrophobic TGF-β inhibitor and an adenovirus gene vector to tumor sites. This co-delivery system sustainably released TGF-β inhibitor SB-505124 and effectively transferred the adenovirus vector carrying the interleukin-12 gene...
May 5, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28441861/anionic-polymer-and-quantum-dot-excipients-to-facilitate-sirna-release-and-self-reporting-of-disassembly-in-stimuli-responsive-nanocarrier-formulations
#9
Chad T Greco, Jason C Andrechak, Thomas H Epps, Millicent O Sullivan
The incorporation of anionic excipients into polyplexes is a promising strategy for modulating siRNA binding versus release and integrating diagnostic capabilities; however, specific design criteria and structure-function relationships are needed to facilitate the development of nanocarrier-based theranostics. Herein, we incorporated poly(acrylic acid) (PAA) and quantum dot (QD) excipients into photolabile siRNA polyplexes to increase gene silencing efficiencies by up to 100% and enable self-reporting of nanocarrier disassembly...
May 10, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28423213/systemic-tumor-targeted-sodium-iodide-symporter-nis-gene-therapy-of-hepatocellular-carcinoma-mediated-by-b6-peptide-polyplexes
#10
Sarah Urnauer, Kathrin Klutz, Geoffrey K Grünwald, Stephan Morys, Nathalie Schwenk, Christian Zach, Franz-Josef Gildehaus, Wolfgang Rödl, Manfred Ogris, Ernst Wagner, Christine Spitzweg
BACKGROUND: Nonviral polymer-based gene transfer represents an adaptable system for tumor-targeted gene therapy because various design strategies of shuttle systems, together with the mechanistic concept of active tumor targeting, lead to improved gene delivery vectors resulting in higher tumor specificity, efficacy and safety. METHODS: Using the sodium iodide symporter (NIS) as a theranostic gene, nonviral gene delivery vehicles based on linear polyethylenimine (LPEI), polyethylene glycol (PEG) and coupled to the synthetic peptide B6 (LPEI-PEG-B6), which specifically binds to tumor cells, were investigated in a hepatocellular carcinoma xenograft model for tumor selectivity and transduction efficiency...
May 2017: Journal of Gene Medicine
https://www.readbyqxmd.com/read/28366646/combinatorial-optimization-of-peg-architecture-and-hydrophobic-content-improves-ternary-sirna-polyplex-stability-pharmacokinetics-and-potency-in-vivo
#11
Thomas A Werfel, Meredith A Jackson, Taylor E Kavanaugh, Kellye C Kirkbride, Martina Miteva, Todd D Giorgio, Craig Duvall
A rationally-designed library of ternary siRNA polyplexes was developed and screened for gene silencing efficacy in vitro and in vivo with the goal of overcoming both cell-level and systemic delivery barriers. [2-(dimethylamino)ethyl methacrylate] (DMAEMA) was homopolymerized or copolymerized (50mol% each) with butyl methacrylate (BMA) from a reversible addition - fragmentation chain transfer (RAFT) chain transfer agent, with and without pre-conjugation to polyethylene glycol (PEG). Both single block polymers were tested as core-forming units, and both PEGylated, diblock polymers were screened as corona-forming units...
June 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28358137/identification-and-evolution-of-a-plant-cell-wall-specific-glycoprotein-glycosyl-transferase-exad
#12
Svenning Rune Møller, Xueying Yi, Silvia Melina Velásquez, Sascha Gille, Pernille Louise Munke Hansen, Christian P Poulsen, Carl Erik Olsen, Martin Rejzek, Harriet Parsons, Yang Zhang, Hans H Wandall, Henrik Clausen, Robert A Field, Markus Pauly, Jose M Estevez, Jesper Harholt, Peter Ulvskov, Bent Larsen Petersen
Extensins are plant cell wall glycoproteins that act as scaffolds for the deposition of the main wall carbohydrate polymers, which are interlocked into the supramolecular wall structure through intra- and inter-molecular iso-di-tyrosine crosslinks within the extensin backbone. In the conserved canonical extensin repeat, Ser-Hyp4, serine and the consecutive C4-hydroxyprolines (Hyps) are substituted with an α-galactose and 1-5 β- or α-linked arabinofuranoses (Arafs), respectively. These modifications are required for correct extended structure and function of the extensin network...
March 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28338690/a-viscous-solvent-enables-information-transfer-from-gene-length-nucleic-acids-in-a-model-prebiotic-replication-cycle
#13
Christine He, Isaac Gállego, Brandon Laughlin, Martha A Grover, Nicholas V Hud
Many hypotheses concerning the nature of early life assume that genetic information was once transferred through the template-directed synthesis of RNA, before the emergence of coded enzymes. However, attempts to demonstrate enzyme-free, template-directed synthesis of nucleic acids have been limited by 'strand inhibition', whereby transferring information from a template strand in the presence of its complementary strand is inhibited by the stability of the template duplex. Here, we use solvent viscosity to circumvent strand inhibition, demonstrating information transfer from a gene-length template (>300 nt) within a longer (545 bp or 3 kb) duplex...
April 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28330769/difference-in-the-core-shell-dynamics-of-polyethyleneimine-and-poly-l-lysine-dna-polyplexes
#14
Elina Vuorimaa-Laukkanen, Ekaterina S Lisitsyna, Tiia-Maaria Ketola, Emmanuelle Morin-Pickardat, Huamin Liang, Martina Hanzlíková, Marjo Yliperttula
Electrostatic polymer-DNA complexes (polyplexes) have been widely investigated for DNA delivery, and remarkable differences in transfection efficacy have been seen among the materials. For example, polyethyleneimine (PEI) mediates DNA transfection more effectively than poly(l-lysine) (PLL). Biophysical properties of the polyplexes may explain their different properties in gene delivery. We investigated the structural dynamics in DNA polyplexes, especially the material exchange between the core and shell regions of the PEI and PLL polyplexes...
March 19, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28327732/properties-of-polyplexes-formed-through-interaction-between-hydrophobically-modified-poly-ethylene-imine-s-and-calf-thymus-dna-in-aqueous-solution
#15
I C Bellettini, S J Fayad, V G Machado, E Minatti
Polycationic polymers and DNA form soluble complexes in aqueous solution, which allows the transfer of genetic material into cells. Therefore, these chemically-modified polymers are of interest for use in studies aimed at better transfection efficiency and gene expression along with reduced cytotoxicity. In this study, branched poly(ethylene imine) (PEI) was modified by alkylation with n-alkyl groups (n = 4, 6, 8 and 12 carbons). The polyplexes formed through interaction of the modified PEIs and calf thymus DNA (ctDNA) were investigated using UV-Vis spectrophotometry, ethidium bromide fluorescence emission, circular dichroism spectroscopy, dynamic light scattering, and small-angle X-ray scattering techniques along with the determination of the zeta potential and viscosity...
March 22, 2017: Soft Matter
https://www.readbyqxmd.com/read/28290156/degradable-polyethylenimine-based-gene-carriers-for-cancer-therapy
#16
REVIEW
Hu-Lin Jiang, Mohammad Ariful Islam, Lei Xing, Jannatul Firdous, Wuji Cao, Yu-Jing He, Yong Zhu, Ki-Hyun Cho, Hui-Shan Li, Chong-Su Cho
Gene therapy using recombinant DNA or gene silencing using siRNA have become a prominent area of research in cancer therapy. However, their use in clinical applications is limited due to overall safety concerns and suboptimal efficacy. Although non-viral vectors such as polycationic polymers do not offer the same level of transfection efficiency as their viral counterparts, they still demonstrate immense potential as alternatives to viral vectors, given their versatility, low immunogenicity, ease of large-scale production, and ability to accelerate gene transfer with well-designed delivery platforms...
April 2017: Topics in Current Chemistry (Journal)
https://www.readbyqxmd.com/read/28284104/development-of-switchable-polymers-to-address-the-dilemma-of-stability-and-cargo-release-in-polycationic-nucleic-acid-carriers
#17
Yilong Cheng, Drew L Sellers, James-Kevin Y Tan, David J Peeler, Philip J Horner, Suzie H Pun
Cationic polymer gene delivery vehicles that effectively resist premature serum degradation often have difficulty releasing their nucleic acid cargoes. In this work, we report a pH-sensitive polymer (SP), poly(oligo(ethylene glycol) monomethyl ether methacrylate)-co-poly(2-(dimethylamino)ethyl methacrylate)-block- poly(propargyl methacrylate-graft-propyl-(4-methoxy-benzylidene)-amine) (p(PMA-PMBA)-b-(p(OEGMA-DMAEMA)), for successful in vitro and in vivo gene transfer. In the physiological condition, the hydrophobization of p(OEGMA-DMAEMA) polycations by p(PMA-PMBA) significantly enhanced the stability of its polyplexes counterpart...
May 2017: Biomaterials
https://www.readbyqxmd.com/read/28181193/history-of-polymeric-gene-delivery-systems
#18
REVIEW
Peng Zhang, Ernst Wagner
As an option for genetic disease treatment and an alternative for traditional cancer chemotherapy, gene therapy achieves significant attention. Nucleic acid delivery, however, remains a main challenge in human gene therapy. Polymer-based delivery systems offer a safer and promising route for therapeutic gene delivery. Over the past five decades, various cationic polymers have been optimized for increasingly effective nucleic acid transfer. This resulted in a chemical evolution of cationic polymers from the first-generation polycations towards bioinspired multifunctional sequence-defined polymers and nanocomposites...
April 2017: Topics in Current Chemistry (Journal)
https://www.readbyqxmd.com/read/28103676/complete-tetrasaccharide-repeat-unit-biosynthesis-of-the-immunomodulatory-bacteroides-fragilis-capsular-polysaccharide-a
#19
Sunita Sharma, Katelyn M Erickson, Jerry M Troutman
Capsular polysaccharide A (CPSA) is a four-sugar repeating unit polymer found on the surface of the gut symbiont Bacteroides fragilis that has therapeutic potential in animal models of autoimmune disorders. This therapeutic potential has been credited to its zwitterionic character derived from a positively charged N-acetyl-4-aminogalactosamine (AADGal) and a negatively charged 4,6-O-pyruvylated galactose (PyrGal). In this report, using a fluorescent polyisoprenoid chemical probe, the complete enzymatic assembly of the CPSA tetrasaccharide repeat unit is achieved...
January 20, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28100091/the-effects-of-polyethylenimine-dna-nanoparticle-on-transcript-levels-of-apoptosis-related-genes
#20
Elham Pishavar, Mohammad Shafiei, Soghra Mehri, Mohammad Ramezani, Khalil Abnous
CONTEXT: Polyethylenimine (PEI) is a cationic polymer commonly used in gene transfer. Although numerous investigations have indicated that PEI can induce apoptosis/necrosis but the mechanism of its cytotoxicity is still poorly understood. OBJECTIVE: The purpose of this study was to investigate the effects of PEI/DNA complexes on the expression of apoptotic genes in human colon adenocarcinoma cells (HT29). METHODS: HT29 cells were exposed to PEI/DNA complex (C/P = 0...
January 18, 2017: Drug and Chemical Toxicology
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