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https://www.readbyqxmd.com/read/28732241/generation-of-skeletal-myogenic-progenitors-from-human-pluripotent-stem-cells-using-non-viral-delivery-of-minicircle-dna
#1
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
https://www.readbyqxmd.com/read/28727419/next-generation-lipids-in-rna-interference-therapeutics
#2
Stephanie Rietwyk, Dan Peer
RNA is emerging as a potential therapeutic modality for the treatment of incurable diseases. Despite intense research, the advent to clinical utility remains compromised by numerous biological barriers, hence there is a need for sophisticated delivery vehicles. In this aspect, lipid nanoparticles (LNP) are the most advanced platform among non-viral vectors for gene delivery. In this review, we critically review the literature and the reasons for ineffective delivery beyond the liver. We discuss the toxicity issues associated with permanently charged cationic lipids, and then turn our attention to next-generation ionizable cationic lipids...
July 20, 2017: ACS Nano
https://www.readbyqxmd.com/read/28725230/genetics-and-genomics-of-cotton-leaf-curl-disease-its-viral-causal-agents-and-whitefly-vector-a-way-forward-to-sustain-cotton-fiber-security
#3
REVIEW
Mehboob-Ur- Rahman, Ali Q Khan, Zainab Rahmat, Muhammad A Iqbal, Yusuf Zafar
Cotton leaf curl disease (CLCuD) after its first epidemic in 1912 in Nigeria, has spread to different cotton growing countries including United States, Pakistan, India, and China. The disease is of viral origin-transmitted by the whitefly Bemisia tabaci, which is difficult to control because of the prevalence of multiple virulent viral strains or related species. The problem is further complicated as the CLCuD causing virus complex has a higher recombination rate. The availability of alternate host crops like tomato, okra, etc...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28722044/tripartite-polyionic-complex-pic-micelles-as-non-viral-vectors-for-mesenchymal-stem-cell-sirna-transfection
#4
Sophie Raisin, Marie Morille, Claire Bony, Danièle Noël, Jean-Marie Devoisselle, Emmanuel Belamie
In the context of regenerative medicine, the use of RNA interference mechanisms has already proven its efficiency in targeting specific gene expression with the aim of enhancing, accelerating or, more generally, directing stem cell differentiation. However, achievement of good transfection levels requires the use of a gene vector. For in vivo applications, synthetic vectors are an interesting option to avoid possible issues associated with viral vectors (safety, production costs, etc.). Herein, we report on the design of tripartite polyionic complex micelles as original non-viral polymeric vectors suited for mesenchymal stem cell transfection with siRNA...
July 19, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28713896/an-optimized-gene-transfection-system-in-weri-rb1-cells
#5
Ying Liu, Zhigang Fan, Kang Li, Fei Deng, Yunfan Xiong, Meixin Liang, Jian Ge
The pathogenesis of Rb1 gene inactivation indicates that gene therapy could be a promising treatment for retinoblastoma. An appropriate gene transfer system is the basis for successful gene therapy; however, little attention has been given to an effective gene transfer system for retinoblastoma therapy in previous studies. This study was designed to provide an optimized transgene system for WERI‑Rb1 cells (W-RBCs). Green fluorescent protein (GFP) was adopted as a reporter. Four classic viral vectors based on retroviruses, recombinant adeno-associated viruses (rAAV2, rAAV2/1), lentiviruses (LVs) and a novel non-viral vector X-treme HP reagent were adopted for W-RBC gene transfection...
July 6, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28711601/catecholaminergic-a1-c1-neurons-contribute-to-the-maintenance-of-upper-airway-muscle-tone-but-may-not-participate-in-nrem-sleep-related-depression-of-these-muscles
#6
Irma Rukhadze, Nancy J Carballo, Sathyajit S Bandaru, Atul Malhotra, Patrick M Fuller, Victor B Fenik
Neural mechanisms of obstructive sleep apnea, a common sleep-related breathing disorder, are incompletely understood. Hypoglossal motoneurons, which provide tonic and inspiratory activation of genioglossus (GG) muscle (a major upper airway dilator), receive catecholaminergic input from medullary A1/C1 neurons. We aimed to determine the contribution of A1/C1 neurons in control of GG muscle during sleep and wakefulness. To do so, we placed injections of a viral vector into DBH-cre mice to selectively express the hMD4i inhibitory chemoreceptors in A1/C1 neurons...
July 12, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28710608/vaccine-platform-recombinant-measles-virus
#7
REVIEW
Michael D Mühlebach
The classic development of vaccines is lengthy, tedious, and may not necessarily be successful as demonstrated by the case of HIV. This is especially a problem for emerging pathogens that are newly introduced into the human population and carry the inherent risk of pandemic spread in a naïve population. For such situations, a considerable number of different platform technologies are under development. These are also under development for pathogens, where directly derived vaccines are regarded as too complicated or even dangerous due to the induction of inefficient or unwanted immune responses causing considerable side-effects as for dengue virus...
July 14, 2017: Virus Genes
https://www.readbyqxmd.com/read/28702475/deletion-of-the-virion-host-shut-off-gene-enhances-neuronal-selective-transgene-expression-from-an-hsv-vector-lacking-functional-ie-genes
#8
Yoshitaka Miyagawa, Gianluca Verlengia, Bonnie Reinhart, Fang Han, Hiroaki Uchida, Silvia Zucchini, William F Goins, Michele Simonato, Justus B Cohen, Joseph C Glorioso
The ability of herpes simplex virus (HSV) to establish lifelong latency in neurons suggests that HSV-derived vectors hold promise for gene delivery to the nervous system. However, vector toxicity and transgene silencing have created significant barriers to vector applications to the brain. Recently, we described a vector defective for all immediate-early gene expression and deleted for the joint region between the two unique genome segments that proved capable of extended transgene expression in non-neuronal cells...
September 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28702043/adoption-of-the-2a-ribosomal-skip-principle-to-tobacco-mosaic-virus-for-peptide-display
#9
Juliane Röder, Rainer Fischer, Ulrich Commandeur
Plant viruses are suitable as building blocks for nanomaterials and nanoparticles because they are easy to modify and can be expressed and purified using plants or heterologous expression systems. Plant virus nanoparticles have been utilized for epitope presentation in vaccines, for drug delivery, as nanospheres and nanowires, and for biomedical imaging applications. Fluorescent protein fusions have been instrumental for the tagging of plant virus particles. The monomeric non-oxygen-dependent fluorescent protein iLOV can be used as an alternative to green fluorescent protein...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28700677/human-adenovirus-type-5-vectors-deleted-of-early-region-1-e1-undergo-limited-expression-of-early-replicative-e2-proteins-and-dna-replication-in-non-permissive-cells
#10
Bratati Saha, Robin J Parks
Adenovirus (Ad) vectors deleted of the early region 1 (E1) are widely used for transgene delivery in preclinical and clinical gene therapy studies. Although proteins encoded within the E1 region are required for efficient virus replication, previous studies have suggested that certain viral or cellular proteins can functionally compensate for E1, leading to expression of the early region 2 (E2)-encoded replicative proteins and subsequent virus replication. We have generated a series of E1-encoding and E1-deficient Ad vectors containing a FLAG-epitope tag on each of the E2-encoded proteins: DNA-binding protein (DBP), terminal protein (TP) and DNA polymerase (Pol)...
2017: PloS One
https://www.readbyqxmd.com/read/28699530/gene-delivery-with-organic-electronic-biomaterials
#11
Kathryn Frances Anne Clancy, John George Hardy
Gene therapy may be capable of treating a variety of diseases, a prerequisite of which is the successful delivery of polynucleic acids (e.g., DNA, RNA) to a patient's cells. Delivery can be achieved technologically (e.g., using electroporation), using viruses (natural gene delivery vectors) or non-viral vectors (e.g., lipids, nanoparticles, polymers). This article aims to give the reader an overview of the use of organic electronic materials (i.e., fullerenes, graphenes and conjugated polymers) as non-viral gene delivery vectors...
July 10, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28692052/disrupting-g6pd-mediated-redox-homeostasis-enhances-chemosensitivity-in-colorectal-cancer
#12
H-Q Ju, Y-X Lu, Q-N Wu, J Liu, Z-L Zeng, H-Y Mo, Y Chen, T Tian, Y Wang, T-B Kang, D Xie, M-S Zeng, P Huang, R-H Xu
Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme that generates NADPH to maintain reduced glutathione (GSH), which scavenges reactive oxygen species (ROS) to protect cancer cell from oxidative damage. In this study, we mainly investigate the potential roles of G6PD in colorectal cancer (CRC) development and chemoresistance. We discover that G6PD is overexpressed in CRC cells and patient specimens. High expression of G6PD predicts poor prognosis and correlated with poor outcome of oxaliplatin-based first-line chemotherapy in patients with CRC...
July 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28689100/synthesis-and-characterization-of-amino-acid-functionalized-calcium-phosphate-nanoparticles-for-sirna-delivery
#13
Feray Bakan, Goknur Kara, Melike Cokol Cakmak, Murat Cokol, Emir Baki Denkbas
Small interfering RNAs (siRNA) are short nucleic acid fragments of about 20-27 nucleotides, which can inhibit the expression of specific genes. siRNA based RNAi technology has emerged as a promising method for the treatment of a variety of diseases. However, a major limitation in the therapeutic use of siRNA is its rapid degradation in plasma and cellular cytoplasm, resulting in short half-life. In addition, as siRNA molecules cannot penetrate into the cell efficiently, it is required to use a carrier system for its delivery...
June 27, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28681841/recombinant-elastin-based-nanoparticles-for-targeted-gene-therapy
#14
D A Monfort, P Koria
Among viruses, lentiviral vectors have been popular vectors for gene delivery due to their efficient mode of gene delivery. However, the non-specific delivery of genes associated with lentiviral vectors may result in undesirable side effects. Here, we propose a heterogeneous nanoparticle delivery system for targeted delivery of lentiviral particles containing a therapeutic gene. The heterogeneous nanoparticles consist of the low density lipoprotein receptor 3 (LDLR3) and the keratinocyte growth factor (KGF), each fused to elastin-like-polypeptides (ELPs), LDLR3-ELP and KGF-ELP, respectively...
July 5, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28677774/construction-of-a-recombinant-lentivirus-mediated-shrna-expression-vector-targeting-the-human-psmd10-gene-and-validation-of-rnai-efficiency-in-rpmi%C3%A2-8226-multiple-myeloma-cells
#15
Siyue Du, Wenjiao Qin, Haiyan Leng, Zi Chen, Tao Zhang
Multiple myeloma (MM) is one of the most common malignant blood cancers. Previous studies have reported that proteasome 26S subunit non-ATPase 10 (PSMD10) is an oncoprotein with complex roles in hepatocellular carcinoma and other malignant tumors. Notably, research on the relationship between PSMD10 and tumorigenesis of MM has rarely been reported. The present study was designed to explore the possibility of PSMD10 as a therapeutic target in the treatment of MM, and the use of RNA interference (RNAi) to determine the function PSMD10...
June 30, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28677531/generation-of-a-human-induced-pluripotent-stem-cell-line-from-urinary-cells-of-a-healthy-donor-using-integration-free-sendai-virus-technology
#16
Bella Rossbach, Laura Hildebrand, Linda El-Ahmad, Harald Stachelscheid, Petra Reinke, Andreas Kurtz
We have generated a human induced pluripotent stem cell (iPSC) line derived from urinary cells of a 28year old healthy female donor. The cells were reprogrammed using a non-integrating viral vector and have shown full differentiation potential. Together with the iPSC line, the donor provided blood cells for the study of immunological effects of the iPSC line and its derivatives in autologous and allogeneic settings. The line is available and registered in the human pluripotent stem cell registry as BCRTi005-A...
May 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28676109/comparative-genomics-shows-that-viral-integrations-are-abundant-and-express-pirnas-in-the-arboviral-vectors-aedes-aegypti-and-aedes-albopictus
#17
Umberto Palatini, Pascal Miesen, Rebeca Carballar-Lejarazu, Lino Ometto, Ettore Rizzo, Zhijian Tu, Ronald P van Rij, Mariangela Bonizzoni
BACKGROUND: Arthropod-borne viruses (arboviruses) transmitted by mosquito vectors cause many important emerging or resurging infectious diseases in humans including dengue, chikungunya and Zika. Understanding the co-evolutionary processes among viruses and vectors is essential for the development of novel transmission-blocking strategies. Episomal viral DNA fragments are produced from arboviral RNA upon infection of mosquito cells and adults. Additionally, sequences from insect-specific viruses and arboviruses have been found integrated into mosquito genomes...
July 5, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28673553/hiv-1-sequence-necessary-and-sufficient-to-package-non-viral-rnas-into-hiv-1-particles
#18
Yang Liu, Olga A Nikolaitchik, Sheikh Abdul Rahman, Jianbo Chen, Vinay K Pathak, Wei-Shau Hu
Genome packaging is an essential step to generate infectious HIV-1 virions and is mediated by interactions between the viral protein Gag and cis-acting elements in the full-length RNA. The sequence necessary and sufficient to allow RNA genome packaging into an HIV-1 particle has not been defined. Here, we used two distinct reporter systems to determine the HIV-1 sequence required for heterologous, non-viral RNAs to be packaged into viral particles. Although the 5' untranslated region (UTR) of the HIV-1 RNA is known to be important for RNA packaging, we found that its ability to mediate packaging relies heavily on the context of the downstream sequences...
June 30, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28672000/synthesis-and-evaluation-of-l-arabinose-based-cationic-glycolipids-as-effective-vectors-for-pdna-and-sirna-in-vitro
#19
Bo Li, Wanrong Guo, Fan Zhang, Meiyan Liu, Shang Wang, Zhonghua Liu, Shuanglin Xiang, Youlin Zeng
Glycolipids might become a new type of promising non-viral gene delivery systems because of their low cytotoxicity, structural diversity, controllable aqua- and lipo-solubility, appropriate density and distribution of positive charges, high transfer efficiency and potential targeting function. In this study, four kinds of L-arabinose-based cationic glycolipids (Ara-DiC12MA, Ara-DiC14MA, Ara-DiC16MA and Ara-DiC18MA) containing quaternary ammonium as hydrophilic headgroup and two alkane chains as hydrophobic domain were synthesized and characterized...
2017: PloS One
https://www.readbyqxmd.com/read/28669112/adeno-associated-virus-aav-as-a-vector-for-gene-therapy
#20
REVIEW
Michael F Naso, Brian Tomkowicz, William L Perry, William R Strohl
There has been a resurgence in gene therapy efforts that is partly fueled by the identification and understanding of new gene delivery vectors. Adeno-associated virus (AAV) is a non-enveloped virus that can be engineered to deliver DNA to target cells, and has attracted a significant amount of attention in the field, especially in clinical-stage experimental therapeutic strategies. The ability to generate recombinant AAV particles lacking any viral genes and containing DNA sequences of interest for various therapeutic applications has thus far proven to be one of the safest strategies for gene therapies...
July 1, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
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