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polymers and gene transfer

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https://www.readbyqxmd.com/read/29125281/brush-like-cationic-polymers-with-low-charge-density-for-gene-delivery
#1
Jonathan O'Keeffe Ahern, Sigen A, Dezhong Zhou, Yongsheng Gao, Jing Lyu, Zhao Meng, Lara Cutlar, Luca Pierucci, Wenxin Wang
Using a combined synthesis approach comprising reversible addition fragmentation transfer (RAFT) polymerization and ring opening reaction (ROR), a series of poly glycidyl methacrylate (polyGMA) polymers were designed and synthesized for gene delivery. These polymers characterised by low cationic charge respective to established gene delivery vectors such as PEI were studied to further elucidate the key structure activity parameters which mediate efficient and biocompatible gene delivery. Compared to PEI these brush-like polymers facilitated markedly improved safety and gene delivery efficiency...
November 10, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/29116801/effects-of-surface-charge-of-hyperbranched-polymers-on-cytotoxicity-dynamic-cellular-uptake-and-localization-hemotoxicity-and-pharmacokinetics-in-mice
#2
Liyu Chen, Joshua D Simpson, Adrian V Fuchs, Barbara E Rolfe, Kristofer J Thurecht
Nanoscaled polymeric materials are increasingly being investigated as pharmaceutical products, drug/gene delivery vectors, or health-monitoring devices. Surface charge is one of the dominant parameters that regulates nanomaterial behavior in vivo. In this paper, we demonstrated how control over chemical synthesis allowed manipulation of nanoparticle surface charge, which in turn greatly influenced the in vivo behavior. Three methacrylate/methacrylamide-based monomers were used to synthesize well-defined hyperbranched polymers (HBP) by reversible addition-fragmentation chain transfer (RAFT) polymerization...
November 8, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29116794/time-resolved-fluorescence-spectroscopy-reveals-fine-structure-and-dynamics-of-poly-l-lysine-and-polyethylenimine-based-dna-polyplexes
#3
Ekaterina S Lisitsyna, Tiia-Maaria Caroline Ketola, Emmanuelle Morin-Picardat, Huamin Liang, Martina Hanzlikova, Arto Urtti, Marjo Yliperttula, Elina Vuorimaa-Laukkanen
Structural dynamics of the polyethyleneimine - DNA and poly(L-lysine) - DNA complexes (polyplexes) was studied by steady-state and time-resolved fluorescence spectroscopy using fluorescence resonance energy transfer (FRET) technique. During the formation of the DNA polyplexes the negative phosphate groups (P) of DNA are bound by the positive amine groups (N) of the polymer. At N/P ratio 2 nearly all the DNA's P-groups are bound by the polymer N groups: these complexes form the core of the polyplexes. The excess polymer, added to this system to increase the N/P ratio to the values giving efficient gene delivery, forms a positively charged shell around the core polyplex...
November 8, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29059528/glycosylated-raft-polymers-with-varying-peg-linkers-produce-different-sirna-uptake-gene-silencing-and-toxicity-profiles
#4
Elizabeth G L Williams, Oliver Earl Hutt, Tracey M Hinton, Sophie C Larnaudie, Tam Le, James M MacDonald, Pathiraja Gunatillake, San H Thang, Peter J Duggan
Achieving efficient and targeted delivery of short interfering (siRNA) is an important research challenge to overcome to render highly promising siRNA therapies clinically successful. Challenges exist in designing synthetic carriers for these RNAi constructs that provide protection against serum degradation, extended blood retention times, effective cellular uptake through a variety of uptake mechanisms, endosomal escape and efficient cargo release. These challenges have resulted in a significant body of research, and led to many important findings about the chemical composition and structural layout of the delivery vector for optimal gene silencing...
October 23, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28943150/screening-and-identification-of-lignin-degrading-bacteria-in-termite-gut-and-the-construction-of-lip-expressing-recombinant-lactococcus-lactis
#5
Haizhu Zhou, Wei Guo, Bo Xu, Zhanwei Teng, Dapeng Tao, Yujie Lou, Yunhang Gao
Lignin, a common natural polymers, is abundant and complex, and termites can break down and utilize the lignin in their food. In this study an attempt was made to isolate and characterize the lignolytic bacteria from termite (Reticulitermes chinensis Snyder) gut. Two strains (PY12 and MX5) with high lignin peroxidase (LiP) activity were screened using the azure B method. By analyzing their 16S rRNA, the strain PY12 was classified as Enterobacter hormaechei; MX5, as Bacillus licheniformis. We then optimized the different conditions of liquid fermentation medium, and obtained LiP activities of 278 U/L and 256 U/L for PY12 and MX5, respectively...
September 21, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28899926/peptides-mediating-dna-transport-on-microtubules-and-their-impact-on-non-viral-gene-transfer-efficiency
#6
REVIEW
Patrick Midoux, Lucie Pigeon, Cristine Gonçalves, Chantal Pichon
Synthetic vectors such as cationic polymers and cationic lipids remain attractive tools for non-viral gene transfer which is a complex process whose effectiveness relies on the ability to deliver a plasmid DNA (pDNA) into the nucleus of non-dividing cells. Once in the cytosol, the transport of pDNAs towards the nuclear envelope is strongly impaired by their very low cytosolic mobility due to their large size. To promote their movement towards the cell nucleus, few strategies have been implemented to exploit dynein, the microtubule's (MT's) motor protein, for propagation of cytosolic pDNA along the MTs towards the cell nucleus...
October 31, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28862422/elaboration-on-the-distribution-of-hydrophobic-segments-in-the-chains-of-amphiphilic-cationic-polymers-for-small-interfering-rna-delivery
#7
Changrong Wang, Lili Du, Junhui Zhou, Lingwei Meng, Qiang Cheng, Chun Wang, Xiaoxia Wang, Deyao Zhao, Yuanyu Huang, Shuquan Zheng, Huiqing Cao, Jianhua Zhang, Liandong Deng, Zicai Liang, Anjie Dong
Hydrophobization of cationic polymers, as an efficient strategy, had been widely developed in the structure of cationic polymer micelles to improve the delivery efficiency of nucleic acids. However, the distribution of hydrophobic segments in the polymer chains is rarely considered. Here, we have elaborated three types of hydrophobized polyethylene glycol (PEG)-blocked cationic polymers with different distributions of the hydrophobic segments in the polymer chains PEG-PAM-PDP (E-A-D), PEG-PDP-PAM (E-D-A), and PEG-P(AM/DP) (E-(A/D)), which were synthesized by reversible addition-fragmentation chain transfer polymerization of methoxy PEG, cationic monomer aminoethyl methacrylate, and pH-sensitive hydrophobic monomer 2-diisopropylaminoethyl methacrylate, respectively...
September 27, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28831252/preparation-characterization-and-transfection-efficiency-of-low-molecular-weight-polyethylenimine-based-nanoparticles-for-delivery-of-the-plasmid-encoding-cd200-gene
#8
Fatemeh Nouri, Hossein Sadeghpour, Reza Heidari, Ali Dehshahri
Various strategies have been utilized to improve both gene transfer efficiency and cell-induced toxicity of polyethylenimine (PEI), the most extensively investigated cationic polymeric vector. In this study, we sought to enhance transfection efficiency of low molecular weight PEI (LMW PEI) while maintaining its low toxicity by cross-linking LMW PEI via succinic acid linker. These modifications were designed to improve the hydrophilic-hydrophobic balance of the polymer, by enhancing the buffering capacity and maintaining low cytotoxic effects of the final conjugate...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28773087/improved-gene-transfer-with-functionalized-hollow-mesoporous-silica-nanoparticles-of-reduced-cytotoxicity
#9
Zhengwen Zhan, Xiaoxu Zhang, Jiayuan Huang, Ying Huang, Zhengwei Huang, Xin Pan, Guilan Quan, Hu Liu, Lili Wang, And Chuanbin Wu
Gene therapy is a promising strategy for treatment of genetically caused diseases. Successful gene delivery requires an efficient carrier to transfer the desired gene into host cells. Recently, mesoporous silica nanoparticles (MSNs) functionalized with 25 kD polyethyleneimine (PEI) were extensively used as gene delivery carriers. However, 25 kD PEI could significantly reduce the safety of the modified MSNs although it is efficient for intracellular delivery of nucleic acids. In addition, limited drug loading remains a challenge for conventional MSNs drug carriers...
June 30, 2017: Materials
https://www.readbyqxmd.com/read/28770290/inorganic-polyphosphate-induces-accelerated-tube-formation-of-huvec-endothelial-cells
#10
Werner E G Müller, Maximilian Ackermann, Shunfeng Wang, Meik Neufurth, Rafael Muñoz-Espí, Qingling Feng, Heinz C Schröder, Xiaohong Wang
In this study, the effect of inorganic polyphosphate (polyP) on the initial phase of angiogenesis and vascularization was investigated, applying the HUVEC cell tube formation assay. PolyP is a physiological and high energy phosphate polymer which has been proposed to act as a metabolic fuel in the extracellular space with only a comparably low ATP content. The experiments revealed that polyP accelerates tube formation of human umbilical vein endothelial cells (HUVEC), seeded onto a solidified basement membrane extract matrix which contains polyP-metabolizing alkaline phosphatase (ALP) activity...
August 2, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28716960/bacterial-tubulins-a-and-b-exhibit-polarized-growth-mixed-polarity-bundling-and-destabilization-by-gtp-hydrolysis
#11
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 (BtubA/B), that have been observed to assemble into filaments in the presence of GTP. BtubA/B polymers are proposed to be composed in vitro by two to six protofilaments in contrast to that in vivo, where they have been reported to form 5-protofilament tubes named bacterial microtubules (bMTs). The btubAB genes likely entered the Prosthecobacter lineage via horizontal gene transfer and may be derived from an early ancestor of the modern eukaryotic microtubule (MT)...
October 1, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28694032/biodegradable-brain-penetrating-dna-nanocomplexes-and-their-use-to-treat-malignant-brain-tumors
#12
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
#13
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
#14
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
#15
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...
2018: Advances in Biochemical Engineering/biotechnology
https://www.readbyqxmd.com/read/28532005/non-viral-strategies-for-ocular-gene-delivery
#16
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
#17
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
#18
Jiayu Jiang, Yuandong Zhang, Ke Peng, Qin Wang, Xiaoyu Hong, Hanmei Li, Gerui Fan, Zhirong Zhang, Tao Gong, Xun Sun
Cancer immunotherapy appears to have 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
#19
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...
June 12, 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
#20
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
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