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polymers and gene transfer

Anne-Laure Chateigner-Boutin, José J Ordaz-Ortiz, Camille Alvarado, Brigitte Bouchet, Sylvie Durand, Yves Verhertbruggen, Yves Barrière, Luc Saulnier
Cell walls are comprised of networks of entangled polymers that differ considerably between species, tissues and developmental stages. The cell walls of grasses, a family that encompasses major crops, contain specific polysaccharide structures such as xylans substituted with feruloylated arabinose residues. Ferulic acid is involved in the grass cell wall assembly by mediating linkages between xylan chains and between xylans and lignins. Ferulic acid contributes to the physical properties of cell walls, it is a hindrance to cell wall degradability (thus biomass conversion and silage digestibility) and may contribute to pest resistance...
2016: Frontiers in Plant Science
Leise Riber, Mette Burmølle, Martin Alm, Stefan M Milani, Peter Thomsen, Lars H Hansen, Søren J Sørensen
The spread of antimicrobial resistance, usually mediated by horizontal transfer of plasmids, limits the options of treating bacterial infections and thereby poses a crucial human health problem. The disturbance of plasmid stability within bacterial species in clinical environments serves as a novel strategy to reduce the development and dissemination of antibiotic resistance. We tested the ability of irgasan to destabilize plasmids from Escherichia coli K-12 cells when added directly into liquid growth medium at concentrations below levels of marked bacterial growth inhibition, or when released into liquid growth medium from irgasan-impregnated Interpenetrating Polymer Network (IPN) silicone hydrogel objects, a novel technology developed as drug-delivery platform...
October 12, 2016: Plasmid
Megan Dearnley, Nicholas P Reynolds, Peter Cass, Xiaohu Wei, Shuning Shi, A Aalam Mohammed, Tam Le, Pathiraja Gunatillake, Mark L Tizard, San H Thang, Tracey M Hinton
The translation of siRNA into clinical therapies has been significantly delayed by issues surrounding the delivery of naked siRNA to target cells. Here we investigate siRNA delivery by cationic acrylic polymers developed by Reversible Addition Fragmentation chain Transfer (RAFT) mediated free radical polymerization. We investigated cell uptake and gene silencing of a series of siRNA-star polymer complexes both in the presence and absence of a protein "corona". Using a multidisciplinary approach including quantitative nanoscale mechanical-atomic force microscopy, dynamic light scattering and nanoparticle tracking analysis we have characterized the nanoscale morphology, stiffness and surface charge of the complexes with and without the protein corona...
October 6, 2016: Biomacromolecules
Moran Golan, Valeria Feinshtein, Ayelet David
The key for successful gene silencing is to design a safe and efficient siRNA delivery system for the transfer of therapeutic nucleic acids into the target cells. Here, we describe the design of hydrophilic N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer displaying multiple copies of octaarginine (R8) and its use in promoting the effective delivery of small interfering RNA (siRNA) molecules intracellularly. Fluorescein-5-isothiocyanate (FITC)-labeled HPMA copolymer-bound R8 (P-R8-FITC) was synthesized with increasing R8 molar ratios (4 to 9...
October 1, 2016: European Journal of Pharmaceutics and Biopharmaceutics
Karen Y P S Avelino, Isaac A M Frias, Norma Lucena-Silva, Renan G Gomes, Celso P de Melo, Maria D L Oliveira, César A S Andrade
In the last ten years, conjugated polymers started to be used in the immobilization of nucleic acids via non-covalent interactions. In the present study, we describe the construction and use of an electrochemical DNA biosensor based on a nanostructured polyaniline-gold composite, specifically developed for the detection of the BCR/ABL chimeric oncogene. This chromosome translocation is used as a biomarker to confirm the clinical diagnosis of both chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL)...
September 22, 2016: Colloids and Surfaces. B, Biointerfaces
Yilong Cheng, Roma C Yumul, Suzie H Pun
Clinical translation of nucleic acids drugs has been stunted by limited delivery options. Herein, we report a synthetic polymer designed to mimic viral mechanisms of delivery called VIPER (virus-inspired polymer for endosomal release). VIPER is composed of a polycation block for condensation of nucleic acids, and a pH-sensitive block for acid-triggered display of a lytic peptide to promote trafficking to the cell cytosol. VIPER shows superior efficiencies compared to commercial agents when delivering genes to multiple immortalized cell lines...
September 19, 2016: Angewandte Chemie
Metin Atila, George Katselis, Paulos Chumala, Yu Luo
Phospholipids generally dominate in bacterial lipids. The negatively charged nature of phospholipids renders bacteria susceptible to cationic antibiotic peptides. In comparison with Gram-negative bacteria, Gram-positive bacteria in general have much less zwitterionic phosphatidylethanolamine. However, they are known for producing aminoacylated phosphatidylglycerol (PG), especially positively charged L-lysyl-PG, which is catalyzed by lysyl-PG synthase MprF, which appears to have a broad range of specificity for L-aminoacyl transfer RNAs...
October 2016: Journal of the American Society for Mass Spectrometry
Qimin Jiang, Yunti Zhang, Renxi Zhuo, Xulin Jiang
This article describes the supramolecular host-guest polycationic gene delivery system based on poly(β-cyclodextrin) (PCD) and azobenzene-terminated polycations. The azobenzene-terminated linear (Az-LPDM) and branched (Az-BPDM) cationic polymers were synthesized by atom transfer radical polymerization (ATRP) of 2-dimethylamino ethyl methacrylate (DMAEMA). The formation and photosensitive behavior of the supramolecular polycations of azobenzene-terminated polycations Az-LPDM and Az-BPDM with PCD were confirmed by UV-vis and NMR analysis...
November 1, 2016: Colloids and Surfaces. B, Biointerfaces
Martin Rother, Martin G Nussbaumer, Kasper Renggli, Nico Bruns
Protein cages are hollow protein nanoparticles, such as viral capsids, virus-like particles, ferritin, heat-shock proteins and chaperonins. They have well-defined capsule-like structures with a monodisperse size. Their protein subunits can be modified by genetic engineering at predetermined positions, allowing for example site-selective introduction of attachment points for functional groups, catalysts or targeting ligands on their outer surface, in their interior and between subunits. Therefore, protein cages have been extensively explored as functional entities in bionanotechnology, as drug-delivery or gene-delivery vehicles, as nanoreactors or as templates for the synthesis of organic and inorganic nanomaterials...
July 18, 2016: Chemical Society Reviews
Chun-Ge Zhang, Shu-di Yang, Wen-Jing Zhu, Ben-Gang You, Yang Liu, Zhi-Qiang Yuan, Wei-Liang Chen, Ji-Zhao Li, Xiao-Feng Zhou, Chun Liu, Xue-Nong Zhang
P-glycoprotein (P-gp) plays an importantrole in multidrug resistance (MDR), proved to be one of the major obstacles in cancer chemotherapy. Cationic polymers could specifically deliver siRNA to tumor cells and thus reverse MDR by the downregulation of P-gp. In this study, a triblock copolymer micelle was prepared based on the polymer of N-succinyl-chitosan-poly-l-lysine-palmitic acid (NSC-PLL-PA) to deliver siRNA-P-gp (siRNA-micelle) or doxorubicin (Dox-micelle). The resulting micelle exhibited an efficient binding ability for siRNA and high encapsulation efficiency for Dox, with an average particle size of ∼170 nm...
July 13, 2016: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
Nathalie Dautin, Célia de Sousa-d'Auria, Florence Constantinesco-Becker, Cécile Labarre, Jacques Oberto, Ines Li de la Sierra-Gallay, Christiane Dietrich, Hanane Issa, Christine Houssin, Nicolas Bayan
Mycobacterium and Corynebacterium are important genera members of the Corynebacteriales order, the members of which are characterized by an atypical diderm cell envelope. Indeed the cytoplasmic membrane of these bacteria is surrounded by a thick mycolic acid-arabinogalactan-peptidoglycan (mAGP) covalent polymer. The mycolic acid-containing part of this complex associates with other lipids (mainly trehalose monomycolate (TMM) and trehalose dimycolate (TDM)) to form an outer membrane. The metabolism of mycolates in the cell envelope is governed by esterases called mycoloyltransferases that catalyze the transfer of mycoloyl chains from TMM to another TMM molecule or to other acceptors such as the terminal arabinoses of arabinogalactan or specific polypeptides...
June 21, 2016: Biochimica et Biophysica Acta
Mehdi Rezaee, Reza Kazemi Oskuee, Hooriyeh Nassirli, Bizhan Malaekeh-Nikouei
Efficient gene therapy is mainly dependent on the gene transfer capability of gene delivery vectors. Non-viral vectors have become the research interest of many researchers because these vectors are safer than viral vectors. Acquiring the advantages of both polyplexes and lipoplexes, the lipopolyplex (LPP) is a ternary nanocomplex composed of cationic liposome, polycation, and nucleic acid. Considering the polycationic component, ternary complexes (LPPs) are divided into cationic polymer-based LPPs and cationic peptide-based LPPs...
August 28, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Linghao Qin, Duanwen Cao, Huan Huang, Gangjian Ji, Min Feng, Jianhai Chen, Shirong Pan
Polyamidoamine (PAMAM) dendrimers are a class of unique nanomaterials which attracted attention because of their extraordinary properties, such as highly branched structure and types of terminal primary groups. In addition, development in PAMAM chemical modification has broadened its biological application especially for drug and gene delivery. In this study, PAMAMs are covalently conjugated onto α-Cyclodextrin (α-CD) via amide bonds obtaining the starburst cationic polymers (CD-PG2). The chemical structure and composition of CD-PG2 was characterized by IH NMR...
February 2016: Journal of Biomedical Nanotechnology
Joann Teo, Joshua A McCarroll, Cyrille Boyer, Janet Youkhana, Sharon M Sagnella, Hien T T Duong, Jie Liu, George Sharbeen, David Goldstein, Thomas P Davis, Maria Kavallaris, Phoebe A Phillips
Pancreatic cancer is a devastating disease with a dismal prognosis. Short-interfering RNA (siRNA)-based therapeutics hold promise for the treatment of cancer. However, development of efficient and safe delivery vehicles for siRNA remains a challenge. Here, we describe the synthesis and physicochemical characterization of star polymers (star 1, star 2, star 3) using reversible addition-fragmentation chain transfer polymerization (RAFT) for the delivery of siRNA to pancreatic cancer cells. These star polymers were designed to contain different lengths of cationic poly(dimethylaminoethyl methacrylate) (PDMAEMA) side-arms and varied amounts of poly[oligo(ethylene glycol) methyl ether methacrylate] (POEGMA)...
July 11, 2016: Biomacromolecules
Joseph Paquet, Adrien Moya, Morad Bensidhoum, Hervé Petite
The treatment of non-unions and bone defects is a major challenge. In these situations, autologous bone is the preferred treatment but has several serious limitations. Treatment alternatives including the use of calcium-based scaffolds alone or associated with either growth factors or stem cells have therefore been developed, or are under development, to overcome these shortcomings. Each of these are, however, associated with their own drawbacks, such as the lack of sustained/controlled delivery system for growth factors and poor cell survival and engraftment for stem cells...
May 2016: Annals of Translational Medicine
Arun R Shrivats, Yuji Mishina, Saadyah Averick, Krzysztof Matyjaszewski, Jeffrey O Hollinger
RNA interference (RNAi) is a powerful tool to treat diseases and elucidate target gene function. Prior to clinical implementation, however, challenges including the safe, efficient and targeted delivery of siRNA must be addressed. Here, we report cationic nanogel nanostructured polymers (NSPs) prepared by atom transfer radical polymerization (ATRP) for in vitro and in vivo siRNA delivery in mammalian models. Outcomes from siRNA protection studies suggested that nanogel NSPs reduce enzymatic degradation of siRNA within polyplexes...
September 2015: Bioengineering
Yoshinori Arisaka, Yuka Nishijima, Shin-Ichi Yusa, Naoya Takeda
We designed photo-crosslinkable polymer brushes with dimethylmaleimide moieties, in order to demonstrate dynamic stimulation of cell differentiation in mesenchymal stem cells (MSCs). The polymer brushes were synthesized by surface-initiated reversible addition fragmentation chain transfer polymerization using dimethylmaleimide ethyl methacrylate and methyl methacrylate on a chain transfer agent-immobilized glass surface. The polymer brushes were crosslinked by photodimerization of the dimethylmaleimide moieties within polymer chains with stem cells present on the surface...
September 2016: Journal of Biomaterials Science. Polymer Edition
Linda Beckert, Libor Kostka, Eva Kessel, Ana Krhac Levacic, Hana Kostkova, Tomas Etrych, Ulrich Lächelt, Ernst Wagner
We report novel pH-reversibly surface-shielded polyplexes with enhanced gene transfer activity upon systemic administration. A four-arm-structured sequence-defined cationic oligomer KK[HK[(H-Sph-K)3HC]2]2 was designed and synthesized on solid-phase, containing additional lysine residues not only for improved pDNA polyplex stability, but also providing attachment points for subsequent polyplex functionalization with amine-reactive shielding polymers. Herein, the surface of polyplexes was shielded with hydrophilic polymers, monovalent PEG or monovalent and multivalent pHPMA, optionally attached to the polyplex via the acid-labile linker AzMMMan...
August 2016: European Journal of Pharmaceutics and Biopharmaceutics
Sara Movassaghian, Yuran Xie, Claudia Hildebrandt, Rayna Rosati, Ying Li, Na Hyung Kim, Denise S Conti, Sandro R P da Rocha, Zeng-Quan Yang, Olivia M Merkel
Basal-like breast cancer (BLBC) accounts for the most aggressive types of breast cancer, marked by high rates of relapse and poor prognoses and with no effective clinical therapy yet. Therefore, investigation of new targets and treatment strategies is more than necessary. Here, we identified a receptor that can be targeted in BLBC for efficient and specific siRNA mediated gene knockdown of therapeutically relevant genes such as the histone demethylase GASC1, which is involved in multiple signaling pathways leading to tumorigenesis...
August 1, 2016: Molecular Pharmaceutics
Nathan Paul Sweeney, Cathy Regan, Jiahui Liu, Antonio Galleu, Francesco Dazzi, Dirk Lindemann, Charles Anthony Rupar, Myra Olga McClure
Mesenchymal stromal cells (MSCs) hold great promise for regenerative medicine. Stable ex vivo gene transfer to MSCs could improve the outcome and scope of MSC therapy, but current vectors require multiple rounds of transduction, involve genotoxic viral promoters and/or the addition of cytotoxic cationic polymers in order to achieve efficient transduction. We describe a self-inactivating foamy virus vector (FVV), incorporating the simian macaque foamy virus envelope and using physiological promoters, which efficiently transduces murine MSCs (mMSCs) in a single-round...
August 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
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