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polymers and gene transfer

Robert Howlett, Katri Anttonen, Nicholas Read, Margaret C M Smith
Actinomycete bacteria use polyprenol phosphate mannose as a lipid linked sugar donor for extra-cytoplasmic glycosyl transferases that transfer mannose to cell envelope polymers, including glycoproteins and glycolipids. We showed recently that strains of Streptomyces coelicolor with mutations in the gene ppm1 encoding polyprenol phosphate mannose synthase were both resistant to phage φC31 and have greatly increased susceptibility to antibiotics that mostly act on cell wall biogenesis. Here we show that mutations in the genes encoding enzymes that act upstream of Ppm1 in the polyprenol phosphate mannose synthesis pathway can also confer phage resistance and antibiotic hyper-susceptibility...
March 1, 2018: Microbiology
Pratheppa Rajagopal, Sowmiya Duraiswamy, Swaminathan Sethuraman, Giridhara R Jayandharan, Uma Maheswari Krishnan
AIM: The advantages and critical aspects of nano-dimensional polymer-coated viral vector systems potentially applicable for gene delivery are reviewed in this article. DISCUSSION: Various viral and non-viral vectors have been explored for gene therapy. Viral gene transfer methods though highly efficient, are limited by their immunogenicity. Non-viral vectors have lower transfection efficiency due to their inability to escape from the endosome. To overcome these drawbacks, novel nanotechnology-mediated interventions that involve coating or modification of virus using polymers have emerged as a new paradigm in gene therapy...
February 8, 2018: Journal of Gene Medicine
I Fernandez-Piñeiro, A Pensado, I Badiola, A Sanchez
Glycosaminoglycans (GAGs) are natural polymers that are broadly used in gene delivery systems to increase stability as well as decrease toxicity and nonspecific interactions, thereby increasing transfection efficiency. In this work, we propose sorbitan ester-based lipid nanoparticles (SENS) functionalised with the GAGs chondroitin sulfate (CS) and hyaluronic acid (HA) as gene delivery systems. For this purpose, we describe the design and evaluation of these nanosystems loaded with plasmid DNA, including an evaluation of their physicochemical characteristics, stability properties, ability to protect and efficiently transfect cells with Enhanced Green Fluorescent Protein plasmid (pEGFP) in vitro, and biocompatibility both in vitro and in vivo...
January 17, 2018: European Journal of Pharmaceutics and Biopharmaceutics
Chi Zhang, Jinkai Ji, Xiaoyan Shi, Xiaoyu Zheng, Xuewei Wang, Fude Feng
Water-soluble conjugated polymers (WCPs) have prospective applications in the field of bioimaging, disease diagnosis and therapy. However, the use of WCPs with controllability and regio-regularity for bioapplications have scarcely been reported. In this work, we synthesized polythiophenes containing ester side chains (P3ET) via Kumada catalyst-transfer polycondensation (KCTP) and confirmed a quasi-"living" chain-growth mechanism. In addition, we obtained cationic regioregular polythiophenes by aminolysis of P3ET with varied chain lengths, and studied DNA binding capability and gene delivery performance...
January 11, 2018: ACS Applied Materials & Interfaces
Liqing Jin, Qing Cai, Wenlin Huang, Keyvan Dastmalchi, Joan Rigau, Marisa Molinas, Mercè Figueras, Olga Serra, Ruth E Stark
Potato native and wound healing periderms contain an external multilayered phellem tissue (potato skin) consisting of dead cells whose cell walls are impregnated with suberin polymers. The phellem provides physical and chemical barriers to tuber dehydration, heat transfer, and pathogenic infection. Previous RNAi-mediated gene silencing studies in native periderm have demonstrated a role for a feruloyl transferase (FHT) in suberin biosynthesis and revealed how its down-regulation affects both chemical composition and physiology...
December 27, 2017: Phytochemistry
Pratyawadee Singhsa, Diana Diaz-Dussan, Hathaikarn Manuspiya, Ravin Narain
Cationic glycopolymers have shown to be excellent candidates for the fabrication of gene delivery devices due to their ability to electrostatically interact with negatively charged nucleic acids and the carbohydrate residues ensure enhanced stability and low toxicity of the polyplexes. The ability to engineer the polymers for optimized compositions, molecular weights, and architectures is critical in the design of effective gene delivery vehicles. Therefore, in this study, the aqueous reversible addition-fragmentation chain transfer polymerization (RAFT) was used to synthesize well-defined cationic glycopolymers with various cationic segments...
January 8, 2018: Biomacromolecules
Zhe Tan, Yogesh K Dhande, Theresa M Reineke
A series of 3-guanidinopropyl methacrylamide (GPMA)-based polymeric gene delivery vehicles were developed via aqueous reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymers have been evaluated for their cellular internalization ability, transfection efficiency, and cytotoxicity. Two homopolymers: P(GPMA20 ), P(GPMA34 ), were synthesized to study the effect of guanidium polymer length on delivery efficiency and toxicity. In addition, an N-acetyl-d-galactosamine (GalNAc)-based hydrophilic block was incorporated to produce diblock polymers, which provides a neutral hydrophilic block that sterically protects plasmid-polymer complexes (polyplexes) from colloidal aggregation and aids polyplex targeting to hepatocytes via binding to asialoglycoprotein receptors (ASGPRs)...
December 20, 2017: Bioconjugate Chemistry
Sarah Urnauer, Andrea M Müller, Christina Schug, Kathrin A Schmohl, Mariella Tutter, Nathalie Schwenk, Wolfgang Rödl, Stephan Morys, Michael Ingrisch, Jens Bertram, Peter Bartenstein, Dirk-André Clevert, Ernst Wagner, Christine Spitzweg
Liver metastases present a serious problem in the therapy of advanced colorectal cancer (CRC), as more than 20% of patients have distant metastases at the time of diagnosis with less than 5% being cured. Consequently, new therapeutic approaches are of major need together with high-resolution imaging methods that allow highly specific detection of small metastases. The unique combination of reporter and therapy gene function of the sodium iodide symporter (NIS) may represent a promising theranostic strategy for CRC liver metastases allowing non-invasive imaging of functional NIS expression and therapeutic application of131 I...
November 3, 2017: Oncotarget
Kisuk Yang, Jin Young Oh, Jong Seung Lee, Yoonhee Jin, Gyeong-Eon Chang, Soo Sang Chae, Eunji Cheong, Hong Koo Baik, Seung-Woo Cho
Optoelectrical manipulation has recently gained attention for cellular engineering; however, few material platforms can be used to efficiently regulate stem cell behaviors via optoelectrical stimulation. In this study, we developed nanoweb substrates composed of photoactive polymer poly(3-hexylthiophene) (P3HT) to enhance the neurogenesis of human fetal neural stem cells (hfNSCs) through photo-induced electrical stimulation. METHODS: The photoactive nanoweb substrates were fabricated by self-assembled one-dimensional (1D) P3HT nanostructures (nanofibrils and nanorods)...
2017: Theranostics
Claudio Campa, Carla Enrica Gallenga, Elena Bolletta, Paolo Perri
Background: Gene therapy represents the therapeutic delivery of nucleic acid polymers into a patient's cells with the aim of treating an underlying disease. Over the past 2 decades this new therapy has made substantial progress owing to better understanding of the pathobiologic basis of various diseases coupled with growth of gene transfer biotechnologies. The eye, in particular, represents a suitable target for such therapy due to the immune privilege provided by the blood-ocular barrier, the ability to directly visualize, access and locally treat the cells and the minimal amount of vector needed given the size of this organ...
November 16, 2017: Current Gene Therapy
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
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...
December 4, 2017: Molecular Pharmaceutics
Ekaterina S Lisitsyna, Tiia-Maaria Ketola, Emmanuelle Morin-Picardat, Huamin Liang, Martina Hanzlíková, Arto Urtti, Marjo Yliperttula, Elina Vuorimaa-Laukkanen
Structural dynamics of the polyethylenimine-DNA and poly(l-lysine)-DNA complexes (polyplexes) was studied by steady-state and time-resolved fluorescence spectroscopy using the 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 of 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...
December 7, 2017: Journal of Physical Chemistry. B
Elizabeth G L Williams, Oliver E 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...
December 11, 2017: Biomacromolecules
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
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
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
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
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
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
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