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https://www.readbyqxmd.com/read/29042259/widespread-optogenetic-expression-in-macaque-cortex-obtained-with-mr-guided-convection-enhanced-delivery-ced-of-aav-vector-to-the-thalamus
#1
Azadeh Yazdan-Shahmorad, Nan Tian, Viktor Kharazia, Lluis Samaranch, Adrian Kells, John Bringas, Jiwei He, Krystof Bankiewicz, Philip N Sabes
BACKGROUND: In non-human primate (NHP) optogenetics, infecting large cortical areas with viral vectors is often a difficult and time-consuming task. Previous work has shown that parenchymal delivery of adeno-associated virus (AAV) in the thalamus by convection-enhanced delivery (CED) can lead to large-scale transduction via axonal transport in distal areas including cortex. We used this approach to obtain widespread cortical expression of light-sensitive ion channels. NEW METHOD: AAV vectors co-expressing channelrhodopsin-2 (ChR2) and yellow fluorescent protein (YFP) genes were infused into thalamus of three rhesus macaques under MR-guided CED...
October 14, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/29040803/synthesis-and-characterization-of-fatty-acid-grafted-chitosan-polymer-and-their-nanomicelles-for-non-viral-gene-delivery-applications
#2
Divya Sharma, Jagdish Singh
The aim of this study was to synthesize and characterize fatty acid-grafted-chitosan (fatty acid-g-CS) polymer and their nanomicelles for using as carriers for gene delivery. CS was hydrophobically modified using saturated fatty acids of increasing fatty acyl chain length. Carbodiimide along with N-hydroxysuccinimide was used for coupling carboxyl group of fatty acids with amine groups of CS. Proton nuclear magnetic resonance and Fourier transform-infrared spectroscopy were used to quantify fatty acyl substitution onto CS backbone...
October 17, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29039731/patchy-dna-forms-of-the-zika-virus-rna-genome-are-generated-following-infection-in-mosquito-cell-cultures-and-in-mosquitoes
#3
Dilip K Nag, Laura D Kramer
Zika virus (ZIKV) is a mosquito-borne flavivirus and has historically been reported to cause mild symptomatic diseases during human infections. More recently, the explosion of microcephaly among infants born to ZIKV-infected women has made ZIKV a global public health concern. While ZIKV causes acute human diseases, infections of vector mosquitoes are basically non-pathogenic, allowing persistent infections and conferring lifelong ability to transmit the virus. Recent studies have revealed that DNA forms of arboviral RNA genomes play a significant role in viral persistence in mosquitoes...
October 17, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/29032724/reintroducing-the-sodium-iodide-symporter-nis-to-anaplastic-thyroid-carcinoma
#4
Kathrin Alexandra Schmohl, Patrick Dolp, Christina Schug, Kerstin Knoop, Kathrin Klutz, Nathalie Schwenk, Peter Bartenstein, Peter Jon Nelson, Manfred Ogris, Ernst Wagner, Christine Spitzweg
Anaplastic thyroid carcinoma (ATC), the most aggressive form of thyroid cancer, is unresponsive to radioiodide therapy. In the current study, we aimed to extend the diagnostic and therapeutic application of radioiodide beyond the treatment of differentiated thyroid cancer by targeting the functional sodium iodide symporter (NIS) to ATC. We employed nanoparticle vectors (polyplexes) based on linear polyethylenimine (LPEI), shielded by polyethylene glycol (PEG) and coupled to the synthetic peptide GE11 as an epidermal growth factor receptor (EGFR)-specific ligand in order to target a <i>NIS</i>-expressing plasmid (LPEI-PEG-GE11/NIS) to EGFR overexpressing human thyroid carcinoma cell lines...
October 15, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/29031848/local-national-and-regional-viral-haemorrhagic-fever-pandemic-potential-in-africa-a-multistage-analysis
#5
David M Pigott, Aniruddha Deshpande, Ian Letourneau, Chloe Morozoff, Robert C Reiner, Moritz U G Kraemer, Shannon E Brent, Isaac I Bogoch, Kamran Khan, Molly H Biehl, Roy Burstein, Lucas Earl, Nancy Fullman, Jane P Messina, Adrian Q N Mylne, Catherine L Moyes, Freya M Shearer, Samir Bhatt, Oliver J Brady, Peter W Gething, Daniel J Weiss, Andrew J Tatem, Luke Caley, Tom De Groeve, Luca Vernaccini, Nick Golding, Peter Horby, Jens H Kuhn, Sandra J Laney, Edmond Ng, Peter Piot, Osman Sankoh, Christopher J L Murray, Simon I Hay
BACKGROUND: Predicting when and where pathogens will emerge is difficult, yet, as shown by the recent Ebola and Zika epidemics, effective and timely responses are key. It is therefore crucial to transition from reactive to proactive responses for these pathogens. To better identify priorities for outbreak mitigation and prevention, we developed a cohesive framework combining disparate methods and data sources, and assessed subnational pandemic potential for four viral haemorrhagic fevers in Africa, Crimean-Congo haemorrhagic fever, Ebola virus disease, Lassa fever, and Marburg virus disease...
October 11, 2017: Lancet
https://www.readbyqxmd.com/read/29031805/aptamer-targeted-delivery-of-bcl-xl-shrna-using-alkyl-modified-pamam-dendrimers-into-lung-cancer-cells
#6
Sara Ayatollahi, Zahra Salmasi, Maryam Hashemi, Saeedeh Askarian, Reza Kazemi Oskuee, Khalil Abnous, Mohammad Ramezani
RNAi-based gene therapy has been recently considered as a promising approach against cancer. Targeted delivery of drug, gene or therapeutic RNAi-based systems to tumor cells is one of the important issues in order to reduce side effects on normal cells. Several strategies have been developed to improve the safety and selectivity of cancer treatments including antibodies, peptides and recently aptamers with various attractive characteristics including higher target specificity, affinity and reduced toxicity...
October 11, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29023541/improved-influenza-viral-vector-based-brucella-abortus-vaccine-induces-robust-b-and-t-cell-responses-and-protection-against-brucella-melitensis-infection-in-pregnant-sheep-and-goats
#7
Aigerim Mailybayeva, Bolat Yespembetov, Sholpan Ryskeldinova, Nadezhda Zinina, Abylai Sansyzbay, Gourapura J Renukaradhya, Nikolai Petrovsky, Kaissar Tabynov
We previously developed a potent candidate vaccine against bovine brucellosis caused by Brucella abortus using the influenza viral vector expressing Brucella Omp16 and L7/L12 proteins (Flu-BA). Our success in the Flu-BA vaccine trial in cattle and results of a pilot study in non-pregnant small ruminants prompted us in the current study to test its efficacy against B. melitensis infection in pregnant sheep and goats. In this study, we improved the Flu-BA vaccine formulation and immunization method to achieve maximum efficacy and safety...
2017: PloS One
https://www.readbyqxmd.com/read/29020107/diacetylenic-lipids-in-the-design-of-stable-lipopolymers-able-to-complex-and-protect-plasmid-dna
#8
C Facundo Temprana, M Jimena Prieto, Daniela E Igartúa, A Lis Femia, M Silvia Amor, Silvia Del Valle Alonso
Different viral and non-viral vectors have been designed to allow the delivery of nucleic acids in gene therapy. In general, non-viral vectors have been associated with increased safety for in vivo use; however, issues regarding their efficacy, toxicity and stability continue to drive further research. Thus, the aim of this study was to evaluate the potential use of the polymerizable diacetylenic lipid 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC8,9PC) as a strategy to formulate stable cationic lipopolymers in the delivery and protection of plasmid DNA...
2017: PloS One
https://www.readbyqxmd.com/read/29019352/hot-news-gene-therapy-with-crispr-cas9-coming-to-age-for-hiv-cure
#9
Vicente Soriano
The huge success of current antiretroviral therapy is mediated by a triple effect: (i) Halting progression to AIDS in infected persons; (ii) reducing the risk of transmission to contacts (treatment as prevention); and (iii) minimizing the risk of HIV acquisition treating uninfected persons at risk (pre-exposure prophylaxis). However, UNAIDS has estimated that only 70% of infected people globally are diagnosed, only 53% are treated, and overall 44% have undetectable viral load, which is the necessary request for ensuring any antiretroviral benefit...
October 11, 2017: AIDS Reviews
https://www.readbyqxmd.com/read/29017848/suppression-of-cotton-leaf-curl-disease-symptoms-in-gossypium-hirsutum-through-over-expression-of-host-encoded-mirnas
#10
Mohd Akmal, Mirza S Baig, Jawaid A Khan
Cotton leaf curl disease (CLCuD), a major factor resulting in the enormous yield losses in cotton crop, is caused by a distinct monopartite begomovirus in association with Cotton leaf curl Multan betasatellite (CLCuMB). Micro(mi)RNAs are known to regulate gene expression in eukaryotes, including antiviral defense in plants. In a previous study, we had computationally identified a set of cotton miRNAs, which were shown to have potential targets in the genomes of Cotton leaf curl Multan virus (CLCuMuV) and CLCuMB at multiple loci...
October 7, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28986940/evaluation-of-a-novel-poly-amidoamine-with-pendant-aminobutyl-group-on-the-cellular-properties-of-transfected-bone-marrow-mesenchymal-stem-cells
#11
Lili Chen, Dan Long, Shishu Huang, Qian Yang, Jing Hao, Nan Wu, Lin Peng
Stem cell-based gene therapy has been considered in the treatment of many degenerative diseases. Gene-modified stem cells should maintain its reproductive activity without losing stem cell properties, including genetic phenotype and differentiation potential. In the study, a novel poly (amidoamine) with pendant aminobutyl group (PAA-BA) designed by our group was used in the transfection of bone marrow mesenchymal stromal cells (BMSCs) and the cellular properties post-transfection were evaluated, including DNA content, colony forming capacity, genetic phenotype and multi-directional differentiation...
October 7, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28982327/comparative-study-of-adeno-associated-virus-adenovirus-baculovirus-and-lentivirus-vectors-for-gene-therapy-of-the-eyes
#12
Giedrius Kalesnykas, Emmi Kokki, Laura Alasaarela, Hanna P Lesch, Timo Tuulos, Kati Kinnunen, Hannu Uusitalo, Kari Airenne, Seppo Ylä-Herttuala
Background The eye possesses unique anatomical features that make it a valuable target for gene therapy applications. Objective The aim of the current study was to compare transduction efficiency, safety and biodistribution of four viral vectors following intravitreal injection. Method Adenovirus (AdV), adeno-associated virus (AAV), baculovirus (BV) and lentivirus (LV) vectors encoding green fluorescent protein (GFP) were injected bilaterally intravitreally into adult C57BL/6OlaHsd mice. Control mice received saline...
October 3, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/28967288/impact-of-itr-integrity-on-raav8-production-using-baculovirus-sf9-cells-system
#13
Adrien Savy, Yohann Dickx, Lucile Nauwynck, Delphine Bonnin, Otto-Wilhelm Merten, Lionel Galibert
The Adeno-Associated Virus (AAV) Inverted Terminal Repeats (ITRs) are key elements of the AAV. These GC rich structures are involved in the replication and encapsidation of the AAV genome, along with its integration in and excision from the host genome. These sequences are the only AAV derived DNA sequences conserved in the recombinant AAV (rAAV) as they allow its replication, encapsidation and long-term maintenance and expression in the target cells. Due to the original vector design, plasmids containing the GOI flanked by ITRs and used for rAAV production often present incomplete, truncated or imperfect ITR sequences...
October 1, 2017: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/28966790/a-biomaterial-approach-to-cell-reprogramming-and-differentiation
#14
Joseph Long, Hyejin Kim, Dajeong Kim, Jong Bum Lee, Deok-Ho Kim
Cell reprogramming of somatic cells into pluripotent states and subsequent differentiation into certain phenotypes has helped progress regenerative medicine research and other medical applications. Recent research has used viral vectors to induce this reprogramming; however, limitations include low efficiency and safety concerns. In this review, we discuss how biomaterial methods offer potential avenues for either increasing viability and downstream applicability of viral methods, or providing a safer alternative...
April 7, 2017: Journal of Materials Chemistry. B, Materials for Biology and Medicine
https://www.readbyqxmd.com/read/28964254/fangorn-forest-f2-a-machine-learning-approach-to-classify-genes-and-genera-in-the-family-geminiviridae
#15
José Cleydson F Silva, Thales F M Carvalho, Elizabeth P B Fontes, Fabio R Cerqueira
BACKGROUND: Geminiviruses infect a broad range of cultivated and non-cultivated plants, causing significant economic losses worldwide. The studies of the diversity of species, taxonomy, mechanisms of evolution, geographic distribution, and mechanisms of interaction of these pathogens with the host have greatly increased in recent years. Furthermore, the use of rolling circle amplification (RCA) and advanced metagenomics approaches have enabled the elucidation of viromes and the identification of many viral agents in a large number of plant species...
September 30, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28960187/genome-engineering-a-new-approach-to-gene-therapy-for-neuromuscular-disorders
#16
REVIEW
Christopher E Nelson, Jacqueline N Robinson-Hamm, Charles A Gersbach
For many neuromuscular disorders, including Duchenne muscular dystrophy, spinal muscular atrophy and myotonic dystrophy, the genetic causes are well known. Gene therapy holds promise for the treatment of these monogenic neuromuscular diseases, and many such therapies have made substantial strides toward clinical translation. Recently, genome engineering tools, including targeted gene editing and gene regulation, have become available to correct the underlying genetic mutations that cause these diseases. In particular, meganucleases, zinc finger nucleases, TALENs, and the CRISPR-Cas9 system have been harnessed to make targeted and specific modifications to the genome...
September 29, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28956174/discovery-of-the-first-maize-infecting-mastrevirus-in-the-americas-using-a-vector-enabled-metagenomics-approach
#17
Rafaela S Fontenele, Dione M T Alves-Freitas, Pedro I T Silva, Josemar Foresti, Paulo R Silva, Márcio T Godinho, Arvind Varsani, Simone G Ribeiro
The genus Mastrevirus (family Geminiviridae) is composed of single-stranded DNA viruses that infect mono- and dicotyledonous plants and are transmitted by leafhoppers. In South America, there have been only two previous reports of mastreviruses, both identified in sweet potatoes (from Peru and Uruguay). As part of a general viral surveillance program, we used a vector-enabled metagenomics (VEM) approach and sampled leafhoppers (Dalbulus maidis) in Itumbiara (State of Goiás), Brazil. High-throughput sequencing of viral DNA purified from the leafhopper sample revealed mastrevirus-like contigs...
September 27, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28955344/what-have-we-learnt-about-bcg-vaccination-in-the-last-20%C3%A2-years
#18
REVIEW
Hazel M Dockrell, Steven G Smith
A number of new tuberculosis (TB) vaccines have been or are entering clinical trials, which include genetically modified mycobacteria, mycobacterial antigens delivered by viral vectors, or mycobacterial antigens in adjuvant. Some of these vaccines aim to replace the existing BCG vaccine but others will be given as a boosting vaccine following BCG vaccination given soon after birth. It is clear that the existing BCG vaccines provide incomplete and variable protection against pulmonary TB. This review will discuss what we have learnt over the last 20 years about how the BCG vaccine induces specific and non-specific immunity, what factors influence the immune responses induced by BCG, and progress toward identifying correlates of immunity against TB from BCG vaccination studies...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28932756/non-clinical-safety-and-efficacy-of-an-aav2-8-vector-administered-intravenously-for-treatment-of-mucopolysaccharidosis-type-vi
#19
Rita Ferla, Marialuisa Alliegro, Jean-Brice Marteau, Margherita Dell'Anno, Edoardo Nusco, Severine Pouillot, Stefania Galimberti, Maria Grazia Valsecchi, Vincent Zuliani, Alberto Auricchio
In vivo gene therapy with adeno-associated viral (AAV) vectors is safe and effective in humans. We recently demonstrated that AAV8-mediated liver gene transfer is effective in animal models of mucopolysaccharidosis type VI (MPS VI), a rare lysosomal storage disease that is caused by arylsulfatase B (ARSB) deficiency. In preparing for a first-in-human trial, we performed non-clinical studies to assess the safety of intravenous administrations of AAV2/8.TBG.hARSB produced under good manufacturing practice-like conditions...
September 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28931684/zika-virus-encoding-non-glycosylated-envelope-protein-is-attenuated-and-defective-in-neuroinvasion
#20
Arun S Annamalai, Aryamav Pattnaik, Bikash R Sahoo, Ezhumalai Muthukrishnan, Sathish Kumar Natarajan, David Steffen, Hiep L X Vu, Gustavo Delhon, Fernando A Osorio, Thomas M Petro, Shi-Hua Xiang, Asit K Pattnaik
Zika virus (ZIKV), a mosquito-transmitted flavivirus, responsible for sporadic outbreaks of mild and febrile illness in Africa and Asia, re-emerged in the last decade causing serious human diseases including microcephaly, congenital malformations, and Guillain-Barré syndrome. Although genomic and phylogenetic analyses suggest that genetic evolution may have led to enhanced virulence of ZIKV, experimental evidence supporting the role of specific genetic changes in virulence is currently outstanding. One sequence motif, VNDT, containing an N-linked glycosylation site in the envelope (E) protein, is polymorphic, being absent in many of the African isolates while present in all isolates from the recent outbreaks...
September 20, 2017: Journal of Virology
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