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polymers and gene transfer

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https://www.readbyqxmd.com/read/28532005/non-viral-strategies-for-ocular-gene-delivery
#1
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
#2
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...
May 16, 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
#3
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
#4
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
#5
Sarah Urnauer, Kathrin Klutz, Geoffrey K Grünwald, Stephan Morys, Nathalie Schwenk, Christian Zach, Franz-Josef Gildehaus, Wolfgang Roedl, Manfred Ogris, Ernst Wagner, Christine Spitzweg
BACKGROUND: Non-viral polymer-based gene transfer represents an adaptable system for tumor-targeted gene therapy, as 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 theranostic gene, non-viral gene delivery vehicles based on linear polyethylenimine (LPEI), polyethylene glycol (PEG) and coupled with the synthetic peptide B6 (LPEI-PEG-B6), which specifically binds to tumor cells, were investigated in a hepatocellular carcinoma (HCC) xenograft model for tumor-selectivity and transduction efficiency...
April 19, 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
#6
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...
March 31, 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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/28095650/bone-tissue-engineering-in-oral-peri-implant-defects-in-preclinical-in-vivo-research-a-systematic-review-and-meta-analysis
#16
REVIEW
Siddharth Shanbhag, Nikolaos Pandis, Kamal Mustafa, Jens R Nyengaard, Andreas Stavropoulos
Regeneration and establishment of osseointegration within oral peri-implant bone defects remains a clinical challenge. Bone tissue engineering (BTE) is emerging as a promising alternative to autogenous and/or biomaterial-based bone grafting. The objective of this systematic review was to answer the focused question: in animal models, do cell-based BTE strategies enhance bone regeneration and/or implant osseointegration in experimental peri-implant defects, compared to grafting with autogenous bone or only biomaterial scaffolds? Electronic databases were searched for controlled animal studies reporting on peri-implant defects and implantation of mesenchymal stem cells (MSC) or other cells seeded on biomaterial scaffolds, following PRISMA guidelines...
January 17, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28088691/stability-effect-of-cholesterol-poly-acrylic-acid-in-a-stimuli-responsive-polymer-liposome-complex-obtained-from-soybean-lecithin-for-controlled-drug-delivery
#17
M G Simões, P Alves, Manuela Carvalheiro, P N Simões
The development of polymer-liposome complexes (PLCs), in particular for biomedical applications, has grown significantly in the last decades. The importance of these studies comes from the emerging need in finding intelligent controlled release systems, more predictable, effective and selective, for applications in several areas, such as treatment and/or diagnosis of cancer, neurological, dermatological, ophthalmic and orthopedic diseases, gene therapy, cosmetic treatments, and food engineering. This work reports the development and characterization of a pH sensitive system for controlled release based on PLCs...
April 1, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28008251/coating-with-spermine-pullulan-polymer-enhances-adenoviral-transduction-of-mesenchymal-stem-cells
#18
Li Wan, Xinglei Yao, Francesco Faiola, Bojun Liu, Tianyuan Zhang, Yasuhiko Tabata, Hiroyuki Mizuguchi, Shinsaku Nakagawa, Jian-Qing Gao, Robert Chunhua Zhao
Mesenchymal stem cells (MSCs) are adult stem cells with multilineage potential, which makes them attractive tools for regenerative medicine applications. Efficient gene transfer into MSCs is essential not only for basic research in developmental biology but also for therapeutic applications involving gene-modification in regenerative medicine. Adenovirus vectors (Advs) can efficiently and transiently introduce an exogenous gene into many cell types via their primary receptors, the coxsackievirus and adenovirus receptors, but not into MSCs, which are deficient in coxsackievirus and adenovirus receptors expression...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27872011/aminoclay-as-a-highly-effective-cationic-vehicle-for-enhancing-adenovirus-mediated-gene-transfer-through-nanobiohybrid-complex-formation
#19
Soo-Yeon Kim, Sang-Jin Lee, Hyo-Kyung Han, Soo-Jeong Lim
Electrostatic complexation of adenovirus (Ad) with cationic lipids or polymers has been shown to be an effective means for overcoming the limitations of adenoviral vectors and enhancing gene-transfer efficacy. However, such complexation causes cytotoxicity, limiting the use of this strategy. The present study explored the potential of 3-aminopropyl functionalized magnesium phyllosilicate (aminoclay) as a cationic vehicle for improving Ad-mediated gene transfer without inducing cytotoxicity. Aminoclay complexation produced a dose-dependent increase in Ad-mediated transgene expression in both Ad infection-sensitive and -refractory cells, thereby greatly lowering the Ad dose required for transgene expression...
November 18, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27864442/two-trichome-birefringence-like-proteins-mediate-xylan-acetylation-which-is-essential-for-leaf-blight-resistance-in-rice
#20
Yaping Gao, Congwu He, Dongmei Zhang, Xiangling Liu, Zuopeng Xu, Yanbao Tian, Xue-Hui Liu, Shanshan Zang, Markus Pauly, Yihua Zhou, Baocai Zhang
Acetylation is a ubiquitous modification on cell wall polymers, which play a structural role in plant growth and stress defenses. However, the mechanisms for how crop plants accomplish cell wall polymer O-acetylation are largely unknown. Here, we report on the isolation and characterization of two trichome birefringence-like (tbl) mutants in rice (Oryza sativa), which are affected in xylan O-acetylation. ostbl1 and ostbl2 single mutant and the tbl1 tbl2 double mutant displayed a stunted growth phenotype with varied degree of dwarfism...
January 2017: Plant Physiology
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