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https://www.readbyqxmd.com/read/28820323/non-surgical-model-for-alveolar-bone-regeneration-by-bone-morphogenetic-protein-2-7-gene-therapy
#1
Mariko Kawai, Yo-Hei Kataoka, Junya Sonobe, Hiromitsu Yamamoto, Masakazu Inubushi, Takuya Ishimoto, Takayoshi Nakano, Hiroki Maruyama, Jun-Ichi Miyazaki, Toshio Yamamoto, Kazuhisa Bessho, Kiyoshi Ohura
BACKGROUND: Alveolar bone is a critical tissue for tooth retention; however, once alveolar bone is lost, it may not spontaneously regenerate. Currently, bone grafts or artificial bone are commonly used for alveolar bone regeneration therapy. However, these therapies require surgical procedures, which present risks, particularly in aged patients. Therefore, the development of alveolar bone regeneration techniques that do not require surgical procedures is critical. It is well known that stem cells present in the periosteal and periodontal ligament may be induced to differentiate into osteogenic cells...
August 18, 2017: Journal of Periodontology
https://www.readbyqxmd.com/read/28810808/advances-and-challenges-in-cardiovascular-gene-therapy
#2
Seppo Ylä-Herttuala, Johanna Lähteenvuo
25 years of gene therapy have not yet yielded standard therapeutic solutions for clinical use in cardiovascular medicine, but several therapeutic targets have been identified and foundations for future therapies have been set. The safety of viral gene therapy has been established with a wide variety of vectors and transgenes. Adenoviruses and adeno-associated viruses have established their role as vectors of choice for many cardiovascular applications and appropriate viral doses have been established for several tissues and applications...
August 16, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28805798/repeated-aav-mediated-gene-transfer-by-serotype-switching-enables-long-lasting-therapeutic-levels-of-hugt1a1-enzyme-in-a-mouse-model-of-crigler-najjar-syndrome-type-i
#3
L Bočkor, G Bortolussi, A Iaconcig, G Chiaruttini, C Tiribelli, M Giacca, F Benvenuti, L Zentilin, A F Muro
Adeno-associated virus (AAV)-mediated gene therapy is a promising strategy to treat liver-based monogenic diseases. However, two major obstacles limit its success: first, vector dilution in actively dividing cells, such as hepatocytes in neonates/children, due to the non-integrating nature of the vector; second, development of an immune response against the transgene and/or viral vector. Crigler-Najjar Syndrome Type I (CNSI) is a rare monogenic disease with neonatal onset, caused by mutations in the liver-specific UGT1 gene, with toxic accumulation of unconjugated bilirubin in plasma, tissues and brain...
August 14, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28804866/virally-vectored-vaccine-delivery-medical-needs-mechanisms-advantages-and-challenges
#4
Daniel D Pinschewer
Vaccines represent one of the most successful chapters in the history of medicine. Over the past decades, the advent of recombinant cDNA technology has enabled the biomedical community to genetically engineer viruses for vaccine delivery purposes. As a starting point, this review evaluates the unmet medical needs, which drive scientists and industry to exploit such fundamentally new technology for human vaccination. The author discusses the molecular functioning, production and safety profile of replication-competent and -deficient viral vector systems, representing two fundamentally distinct classes of "genetic vaccines"...
August 14, 2017: Swiss Medical Weekly
https://www.readbyqxmd.com/read/28796282/disulfide-bond-containing-agamatine-cystaminebisacrylamide-polymer-demonstrates-better-transfection-efficiency-and-lower-cytotoxicity-than-polyethylenimine-in-nih-3t3-cells
#5
Zhen Yang, Yanping Sun, Lei Xian, Zhe Xun, Jiankun Yu, Tianzhi Yang, Xiaoyun Zhao, Cuifang Cai, Dongkai Wang, Pingtian Ding
Previously, we synthesized a non-viral vector containing disulfide bond by polymerization of agamatine (AGM) and N, N'-cystaminebisacrylamide (CBA). In this study, we investigated the transfection efficiency of disulfide bond (-SS-) containing AGM-CBA polymer in gene delivery into NIH/3T3 cells, and examined the factors affecting its transfection efficiency by comparing with polyethylenimine (PEI). In addition, experiments were carried out to determine the mechanisms of cell entry pathways and intracellular behavior of AGM-CBA/pDNA polyplexes...
August 10, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28776750/generation-of-a-non-transmissive-borna-disease-virus-vector-lacking-both-matrix-and-glycoprotein-genes
#6
Kan Fujino, Yusuke Yamamoto, Takuji Daito, Akiko Makino, Tomoyuki Honda, Keizo Tomonaga
Borna disease virus (BoDV), a prototype of mammalian bornavirus, is a non-segmented, negative strand RNA virus that often causes severe neurological disorders in infected animals, including horses and sheep. Unique among animal RNA viruses, BoDV transcribes and replicates non-cytopathically in the cell nucleus, leading to the establishment of a long-lasting persistent infection. This striking feature of BoDV indicates its potential as an RNA virus vector system. In a previous study, we demonstrated that recombinant BoDV (rBoDV) lacking an envelope glycoprotein (G) gene develops a persistent infection in the transduced cells without loss of the viral genome...
August 4, 2017: Microbiology and Immunology
https://www.readbyqxmd.com/read/28776202/neurotrophin-gene-therapy-in-deafened-ears-with-cochlear-implants-long-term-effects-on-nerve-survival-and-functional-measures
#7
Bryan E Pfingst, Deborah J Colesa, Donald L Swiderski, Aaron P Hughes, Stefan B Strahl, Moaz Sinan, Yehoash Raphael
Because cochlear implants function by stimulating the auditory nerve, it is assumed that the condition of the nerve plays an important role in the efficacy of the prosthesis. Thus, considerable research has been devoted to methods of preserving the nerve following deafness. Neurotrophins have been identified as a potential contributor to neural health, but most of the research to date has been done in young animals and for short periods (less than 3 to 6 months) after the onset of treatment. The first objective of the current experiment was to examine the effects of a neurotrophin gene therapy delivery method on spiral ganglion neuron (SGN) preservation and function in the long term (5 to 14 months) in mature guinea pigs with cochlear implants...
August 3, 2017: Journal of the Association for Research in Otolaryngology: JARO
https://www.readbyqxmd.com/read/28772262/evolution-and-emergence-of-pathogenic-viruses-past-present-and-future
#8
Mohammad K Parvez, Shama Parveen
Incidences of emerging/re-emerging deadly viral infections have significantly affected human health despite extraordinary progress in the area of biomedical knowledge. The best examples are the recurring outbreaks of dengue and chikungunya fever in tropical and sub-tropical regions, the recent epidemic of Zika in the Americas and the Caribbean, and the SARS, MERS, and influenza A outbreaks across the globe. The established natural reservoirs of human viruses are mainly farm animals, and, to a lesser extent, wild animals and arthropods...
August 4, 2017: Intervirology
https://www.readbyqxmd.com/read/28771513/a-modified-vaccinia-ankara-vaccine-vector-expressing-a-mosaic-h5-hemagglutinin-reduces-viral-shedding-in-rhesus-macaques
#9
Nicholas W Florek, Attapon Kamlangdee, James P Mutschler, Brock Kingstad-Bakke, Nancy Schultz-Darken, Karl W Broman, Jorge E Osorio, Thomas C Friedrich
The rapid antigenic evolution of influenza viruses requires frequent vaccine reformulations. Due to the economic burden of continuous vaccine reformulation and the threat of new pandemics, there is intense interest in developing vaccines capable of eliciting broadly cross-reactive immunity to influenza viruses. We recently constructed a "mosaic" hemagglutinin (HA) based on subtype 5 HA (H5) and designed to stimulate cellular and humoral immunity to multiple influenza virus subtypes. Modified vaccinia Ankara (MVA) expressing this H5 mosaic (MVA-H5M) protected mice against multiple homosubtypic H5N1 strains and a heterosubtypic H1N1 virus...
2017: PloS One
https://www.readbyqxmd.com/read/28771235/systemic-gene-delivery-transduces-the-enteric-nervous-system-of-guinea-pigs-and-cynomolgus-macaques
#10
S E Gombash, C J Cowley, J A Fitzgerald, C A Lepak, M G Neides, K Hook, L J Todd, G-D Wang, C Mueller, B K Kaspar, E C Bielefeld, A J Fischer, J D Wood, K D Foust
Characterization of adeno-associated viral vector (AAV) mediated gene delivery to the enteric nervous system (ENS) was recently described in mice and rats. In these proof-of-concept experiments, we show that intravenous injections of clinically relevant AAVs can transduce the ENS in guinea pigs and non-human primates. Neonatal guinea pigs were given intravenous injections of either AAV8 or AAV9 vectors that contained a green fluorescent protein (GFP) expression cassette or PBS. Piglets were euthanized three weeks post-injection and tissues were harvested for immunofluorescent analysis...
August 3, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28769903/covert-infection-of-insects-by-baculoviruses
#11
REVIEW
Trevor Williams, Cristina Virto, Rosa Murillo, Primitivo Caballero
Baculoviruses (Baculoviridae) are occluded DNA viruses that are lethal pathogens of the larval stages of some lepidopterans, mosquitoes, and sawflies (phytophagous Hymenoptera). These viruses have been developed as biological insecticides for control of insect pests and as expression vectors in biotechnological applications. Natural and laboratory populations frequently harbor covert infections by baculoviruses, often at a prevalence exceeding 50%. Covert infection can comprise either non-productive latency or sublethal infection involving low level production of virus progeny...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28768856/non-encapsidated-5-copy-back-defective-interfering-genomes-produced-by-recombinant-measles-viruses-are-recognized-by-rig-i-and-lgp2-but-not-mda5
#12
Marie Mura, Chantal Combredet, Valérie Najburg, Raul Y Sanchez David, Frédéric Tangy, Anastassia V Komarova
Attenuated Measles virus (MV) is one of the most effective and safe vaccine available, making it an attractive candidate vector to prevent other infectious diseases. Yet the great capacity of this vaccine still needs to be understood at the molecular level. MV vaccine strains have different type-I interferon-inducing abilities, that partially depend on the presence of 5' copy-back defective interfering genomes (DI-RNAs). DI-RNAs are pathogen associated molecular patterns recognized by RIG-I-like receptors (RLRs: RIG-I, MDA5 and LGP2) that activate innate immune signalling and shape the adaptive immune response...
August 2, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28752293/development-of-recombinant-yarrowia-lipolytica-producing-virus-like-particles-of-a-fish-nervous-necrosis-virus
#13
Van-Trinh Luu, Hye Yun Moon, Jee Youn Hwang, Bo-Kyu Kang, Hyun Ah Kang
Nervous necrosis virus (NNV) causes viral encephalopathy and retinopathy, a devastating disease of many species of cultured marine fish worldwide. In this study, we used the dimorphic non-pathogenic yeast Yarrowia lipolytica as a host to express the capsid protein of red-spotted grouper nervous necrosis virus (RGNNV-CP) and evaluated its potential as a platform for vaccine production. An initial attempt was made to express the codon-optimized synthetic genes encoding intact and N-terminal truncated forms of RGNNV-CP under the strong constitutive TEF1 promoter using autonomously replicating sequence (ARS)-based vectors...
August 2017: Journal of Microbiology / the Microbiological Society of Korea
https://www.readbyqxmd.com/read/28748978/degradable-polyesters-via-ring-opening-polymerization-of-functional-valerolactones-for-efficient-gene-delivery
#14
Ling Song, Ai-Xiang Ding, Ke-Xin Zhang, Bing Gong, Zhong-Lin Lu, Lan He
Degradable polymers as gene and drug carriers are emerging as one of the most promising types of materials in the biomedical and pharmaceutical areas. Herein, we report the synthesis of a series of block co-polyesters (B1-B6) and random co-polyesters (C1-C4) via ring-opening polymerization of tertiary amine-bearing valerolactone and alkylated valerolactone monomers. These polymers can completely inhibit the electrophoretic migrations of plasmid DNAs (pDNAs) at a w/w ratio of 2-6. The polyplexes of these polymers with pDNAs were steadily formed in a narrow range of sizes (75 to 220 nm) and could be effectively internalized into the cytoplasm...
August 9, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28747494/bam35-tectivirus-intraviral-interaction-map-unveils-new-function-and-localization-of-phage-orfan-proteins
#15
Mónica Berjón-Otero, Ana Lechuga, Jitender Mehla, Peter Uetz, Margarita Salas, Modesto Redrejo-Rodríguez
Tectiviridae comprises a group of tail-less, icosahedral, membrane-containing bacteriophages that can be divided into two groups by their hosts, either Gram-negative or Gram-positive bacteria. While the first group is composed of PRD1 and nearly identical well characterized lytic viruses, the second one includes more variable temperate phages, like GIL16 or Bam35, whose hosts are Bacillus cereus and related Gram-positive bacteria.In the genome of Bam35, nearly half of the 32 annotated open reading frames (ORFs) have no homologs in databases (ORFans), being putative proteins of unknown function, which hinders the understanding of their biology...
July 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28746382/gelatin-nanoparticles-enhance-delivery-of-hepatitis-c-virus-recombinant-ns2-gene
#16
Salwa Sabet, Marina A George, Haidan M El-Shorbagy, Heba Bassiony, Khaled Y Farroh, Tareq Youssef, Taher A Salaheldin
BACKGROUND: Development of an effective non-viral vaccine against hepatitis C virus infection is of a great importance. Gelatin nanoparticles (Gel.NPs) have an attention and promising approach as a viable carrier for delivery of vaccine, gene, drug and other biomolecules in the body. AIM OF WORK: The present study aimed to develop stable Gel.NPs conjugated with nonstructural protein 2 (NS2) gene of Hepatitis C Virus genotype 4a (HCV4a) as a safe and an efficient vaccine delivery system...
2017: PloS One
https://www.readbyqxmd.com/read/28736304/advances-in-cancer-stem-cell-targeting-how-to-strike-the-evil-at-its-root
#17
Brigitte M Pützer, Manish Solanki, Ottmar Herchenröder
Cancer progression to metastatic stages is still unmanageable and the promise of effective anti-metastatic therapy remains largely unmet, emphasizing the need to develop novel therapeutics. The special focus here is on cancer stem cells (CSC) as the seed of tumor initiation, epithelial-mesenchymal transition, chemoresistance and, as a consequence, drivers of metastatic dissemination. We report on targeted therapies gearing towards the CSC's internal and membrane-anchored markers using agents such as antibody derivatives, nucleic therapeutics, small molecules and genetic payloads...
July 21, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28735515/determination-of-cell-fate-in-skeletal-muscle-following-bmp-gene-transfer-by-in-vivo-electroporation
#18
Mariko Kawai, Yu-Ki Ohmori, Mai Nishino, Masayo Yoshida, Kaori Tabata, Do-Saku Hirota, Ayako Ryu-Mon, Hiromitsu Yamamoto, Junya Sonobe, Yo-Hei Kataoka, Noriko Shiotsu, Mika Ikegame, Hiroki Maruyama, Toshio Yamamoto, Kazuhisa Bessho, Kiyoshi Ohura
We previously developed a novel method for gene transfer, which combined a non-viral gene expression vector with transcutaneous in vivo electroporation. We applied this method to transfer the bone morphogenetic protein (BMP) gene and induce ectopic bone formation in rat skeletal muscles. At present, it remains unclear which types of cells can differentiate into osteogenic cells after BMP gene transfer by in vivo electroporation. Two types of stem cells in skeletal muscle can differentiate into osteogenic cells: muscle-derived stem cells, and bone marrow-derived stem cells in the blood...
May 5, 2017: European Journal of Histochemistry: EJH
https://www.readbyqxmd.com/read/28733354/selective-silencing-of-hippocampal-parvalbumin-interneurons-induces-development-of-recurrent-spontaneous-limbic-seizures-in-mice
#19
Meinrad Drexel, Roman A Romanov, James Wood, Stefan Weger, Regine Heilbronn, Peer Wulff, Ramon O Tasan, Tibor Harkany, Günther Sperk
Temporal lobe epilepsy (TLE) is the most frequent form of focal epilepsies and generally associated with malfunctioning of the hippocampal formation. Recently, a preferential loss of parvalbumin (PV) neurons has been observed in the subiculum of TLE patients and in animal models of TLE. To demonstrate a possible causative role of defunct PV neurons in the generation of TLE, we permanently inhibited GABA release selectively from PV neurons of the ventral subiculum by injecting a viral vector expressing tetanus toxin light chain in male mice...
July 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28732241/generation-of-skeletal-myogenic-progenitors-from-human-pluripotent-stem-cells-using-non-viral-delivery-of-minicircle-dna
#20
Jaemin Kim, Vanessa K P Oliveira, Ami Yamamoto, Rita C R Perlingeiro
Currently, the most efficient and promising approach for generating large numbers of engraftable human skeletal myogenic progenitors from pluripotent stem cells requires the conditional in vitro overexpression of PAX7 using lentiviral vectors. Because a non-integrating approach would be preferable to eliminate or minimize the risk associated with random genomic integration, here we investigate whether transient expression of PAX7 using minicircle DNA would enable the generation of functional pluripotent stem cell-derived myogenic progenitors, equivalent to those generated by lentivirus...
July 12, 2017: Stem Cell Research
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