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https://www.readbyqxmd.com/read/29150005/crispr-libraries-and-screening
#1
John T Poirier
CRISPR-Cas9 technology has revolutionized large-scale functional genomic screening in mammalian cell-culture systems. Due in part to optimized lentiviral delivery vectors; it is now possible to perform CRISPR-Cas9 screens in animals in order to study biological processes in the context of a whole organism and within more physiologically relevant environment. This chapter focuses primarily on mouse models of human cancers; viral vectors used for simultaneous tumor initiation and genome editing and sgRNA library design considerations...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/29149775/lentiviral-vectors-and-adeno-associated-virus-vectors-useful-tools-for-gene-transfer-in-pain-research
#2
REVIEW
Zheng Chen-Xi, Wang Sheng-Ming, Bai Yun-Hu, Luo Ting-Ting, Wang Jia-Qi, Dai Chun-Qiu, Guo Bao-Lin, Luo Shi-Cheng, Wang Dong-Hui, Yang Yan-Ling, Wang Ya-Yun
Pain, especially chronic pain, has always been a heated point in both basic and clinical researches since it puts heavy burdens on both individuals and the whole society. A better understanding of the role of biological molecules and various ionic channels involved in pain can shed light on the mechanism under pain and advocate the development of pain management. Using viral vectors to transfer specific genes at targeted sites is a promising method for both research and clinical applications. Lentiviral vectors and adeno-associated virus (AAV) vectors which allow stable and long-term expression of transgene in non-dividing cells are widely applied in pain research...
November 17, 2017: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/29149197/sieve-analysis-of-breakthrough-hiv-1-sequences-in-hvtn-505-identifies-vaccine-pressure-targeting-the-cd4-binding-site-of-env-gp120
#3
Allan C deCamp, Morgane Rolland, Paul T Edlefsen, Eric Sanders-Buell, Breana Hall, Craig A Magaret, Andrew J Fiore-Gartland, Michal Juraska, Lindsay N Carpp, Shelly T Karuna, Meera Bose, Steven LePore, Shana Miller, Annemarie O'Sullivan, Kultida Poltavee, Hongjun Bai, Kalpana Dommaraju, Hong Zhao, Kim Wong, Lennie Chen, Hasan Ahmed, Derrick Goodman, Matthew Z Tay, Raphael Gottardo, Richard A Koup, Robert Bailer, John R Mascola, Barney S Graham, Mario Roederer, Robert J O'Connell, Nelson L Michael, Merlin L Robb, Elizabeth Adams, Patricia D'Souza, James Kublin, Lawrence Corey, Daniel E Geraghty, Nicole Frahm, Georgia D Tomaras, M Juliana McElrath, Lisa Frenkel, Sheila Styrchak, Sodsai Tovanabutra, Magdalena E Sobieszczyk, Scott M Hammer, Jerome H Kim, James I Mullins, Peter B Gilbert
Although the HVTN 505 DNA/recombinant adenovirus type 5 vector HIV-1 vaccine trial showed no overall efficacy, analysis of breakthrough HIV-1 sequences in participants can help determine whether vaccine-induced immune responses impacted viruses that caused infection. We analyzed 480 HIV-1 genomes sampled from 27 vaccine and 20 placebo recipients and found that intra-host HIV-1 diversity was significantly lower in vaccine recipients (P ≤ 0.04, Q-values ≤ 0.09) in Gag, Pol, Vif and envelope glycoprotein gp120 (Env-gp120)...
2017: PloS One
https://www.readbyqxmd.com/read/29146945/maraba-virus-vectored-cancer-vaccines-represent-a-safe-and-novel-therapeutic-option-for-cats
#4
Jeff Hummel, Dorothee Bienzle, Annette Morrison, Michelle Cieplak, Kyle Stephenson, Josepha DeLay, J Paul Woods, Brian D Lichty, Byram W Bridle
Direct killing of malignant cells combined with induction of tumour-specific immune responses makes oncolytic vaccines attractive for cancer therapy. We previously developed a heterologous cancer immunization strategy that utilized a replication-defective adenovirus-vectored primary vaccine encoding a tumour antigen followed by boosting with a replication-competent Maraba virus expressing the same antigen. To assess the safety of oncolytic Maraba virus-based booster vaccines and inform the design of clinical trials, we conducted translational studies in cats, which have immune systems that are similar to people and spontaneously develop cancers of comparable types and etiologies...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29146410/cart-neurons-in-the-arcuate-nucleus-and-lateral-hypothalamic-area-exert-differential-controls-on-energy-homeostasis
#5
Jackie Lau, Aitak Farzi, Yue Qi, Regine Heilbronn, Mario Mietzsch, Yan-Chuan Shi, Herbert Herzog
OBJECTIVE: The cocaine- and amphetamine-regulated transcript (CART) codes for a pivotal neuropeptide important in the control of appetite and energy homeostasis. However, limited understanding exists for the defined effector sites underlying CART function, as discrepant effects of central CART administration have been reported. METHODS: By combining Cart-cre knock-in mice with a Cart adeno-associated viral vector designed using the flip-excision switch (AAV-FLEX) technology, specific reintroduction or overexpression of CART selectively in CART neurons in the arcuate nucleus (Arc) and lateral hypothalamic area (LHA), respectively, was achieved...
November 8, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29145481/amiloride-enhanced-gene-transfection-of-octa-arginine-functionalized-calcium-phosphate-nanoparticles
#6
Juan Ramón Vanegas Sáenz, Taichi Tenkumo, Yuya Kamano, Hiroshi Egusa, Keiichi Sasaki
Nanoparticles represent promising gene delivery systems in biomedicine to facilitate prolonged gene expression with low toxicity compared to viral vectors. Specifically, nanoparticles of calcium phosphate (nCaP), the main inorganic component of human bone, exhibit high biocompatibility and good biodegradability and have been reported to have high affinity for protein or DNA, having thus been used as gene transfer vectors. On the other hand, Octa-arginine (R8), which has a high permeability to cell membrane, has been reported to improve intracellular delivery systems...
2017: PloS One
https://www.readbyqxmd.com/read/29145171/host-target-based-approaches-against-arboviral-diseases
#7
Rebeca Froes Rocha, Juliana Lemos Del Sarto, Rafael Elias Marques, Vivian Vasconcelos Costa, Mauro Martins Teixeira
In the 20th century, socioeconomic and environmental changes facilitated the reintroduction of mosquitoes in developing cities, resulting in the reintroduction of mosquito-borne viral diseases and the dispersal of their causative agents in a worldwide scale. Recurrent outbreaks of arboviral diseases are being reported, even in regions without a previous history of arboviral disease transmission. Of note, arboviral infections represented approximately 30% of all emerging vector-borne diseases of the last decade...
November 27, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/29143186/identification-of-an-anellovirus-and-genomoviruses-in-ixodid-ticks
#8
Kara Waits, Marten J Edwards, Ilaria N Cobb, Rafaela S Fontenele, Arvind Varsani
Ticks are blood-feeding arachnids that are vectors of several important human and animal pathogens. Little is known about single-stranded DNA (ssDNA) viruses that are associated with these ectoparasites. As part of a pilot study to identify ssDNA viruses present in ticks, female American dog ticks (Dermacentor variabilis) and blacklegged ticks (Ixodes scapularis) were collected in eastern Pennsylvania (USA), and the extracted viral DNA was analyzed using viral metagenomics approaches. Three genomoviruses were recovered from pooled samples of D...
November 15, 2017: Virus Genes
https://www.readbyqxmd.com/read/29142017/modelling-the-effects-of-phylogeny-and-body-size-on-within-host-pathogen-replication-and-immune-response
#9
Soumya Banerjee, Alan S Perelson, Melanie Moses
Understanding how quickly pathogens replicate and how quickly the immune system responds is important for predicting the epidemic spread of emerging pathogens. Host body size, through its correlation with metabolic rates, is theoretically predicted to impact pathogen replication rates and immune system response rates. Here, we use mathematical models of viral time courses from multiple species of birds infected by a generalist pathogen (West Nile Virus; WNV) to test more thoroughly how disease progression and immune response depend on mass and host phylogeny...
November 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/29141205/investigation-of-alimentary-canal-ultrastructure-following-knockdown-of-the-dicer-2-gene-in-planthoppers-reveals-the-potential-pathogenicity-of-southern-rice-black-streaked-dwarf-virus-to-its-insect-vector
#10
Yuyan Liu, Qianzhuo Mao, Hanhong Lan, Haitao Wang, Taiyun Wei, Qian Chen
An increasing number of studies are suggesting that plant viruses, including southern rice black-streaked dwarf virus (SRBSDV), can adversely affect biological characteristics of insect vectors by unknown mechanisms. To study the adverse effect of SRBSDV at cellular level on the insect vector, we promoted viral infection by the disruption of the small interfering RNA (siRNA) pathway. The transmission electron microscopy was utilized to describe the ultrastructural changes that occurred in insects when the core component of the siRNA pathway, Dicer-2, was knocked down...
November 12, 2017: Virus Research
https://www.readbyqxmd.com/read/29131357/zika-virus-what-we-need-to-know
#11
REVIEW
Farakh Javed, Khanzadi N Manzoor, Mubashar Ali, Irshad U Haq, Abid A Khan, Assad Zaib, Sobia Manzoor
Zika virus is one of the emerging viruses and is of significant threat to human health globally. It is a mosquito borne flavivirus similar to dengue, yellow fever, and West Nile viruses. It was reported about 5 decades ago and then it spreads to different parts of the world. Large outbreaks were reported on Yap Islands in 2007. Now it has gained wide attention globally by health communities. Major vector for virus transmission is Aedes aegypti mosquito. ZIKV infection is mostly asymptomatic but it is also responsible to cause mild influenza like illness to serious manifestations...
November 13, 2017: Journal of Basic Microbiology
https://www.readbyqxmd.com/read/29130354/delivery-of-adeno-associated-viral-vectors-in-adult-mammalian-inner-ear-cell-subtypes-without-auditory-dysfunction
#12
Yong Tao, Mingqian Huang, Yilai Shu, Adam Ruprecht, Hongyang Wang, Yong Tang, Luk H Vandenberghe, Qiuju Wang, Guangping Gao, Wei-Jia Kong, Zheng-Yi Chen
Hearing loss, including genetic hearing loss, is one of the most common forms of sensory deficits in human with limited options of treatment. Adeno-associated virus (AAV)-mediated gene transfer has been shown to effectively recover auditory functions in mouse models of genetic deafness when delivered at neonatal stages. However, the mouse cochlea is still developing at those time points whereas in human the newborn inner ears are already fully mature. For effective gene therapy to treat genetic deafness, it is necessary to determine whether or not AAV-mediated therapy can be equally effective in the fully mature mouse inner ear without causing damages to the inner ear...
November 12, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29130152/combining-engineered-nucleases-with-adeno-associated-viral-vectors-for-therapeutic-gene-editing
#13
Benjamin E Epstein, David V Schaffer
With the recent advent of several generations of targeted DNA nucleases, most recently CRISPR/Cas9, genome editing has become broadly accessible across the biomedical community. Importantly, the capacity of these nucleases to modify specific genomic loci associated with human disease could render new classes of genetic disease, including autosomal dominant or even idiopathic disease, accessible to gene therapy. In parallel, the emergence of adeno-associated virus (AAV) as a clinically important vector raises the possibility of integrating these two technologies towards the development of gene editing therapies...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29130151/viral-vectors-engineered-cells-and-the-crispr-revolution
#14
James E DiCarlo, Anurag Deeconda, Stephen H Tsang
Over the past few decades the ability to edit human cells has revolutionized modern biology and medicine. With advances in genome editing methodologies, gene delivery and cell-based therapeutics targeted at treatment of genetic disease have become a reality that will become more and more essential in clinical practice. Modifying specific mutations in eukaryotic cells using CRISPR-Cas systems derived from prokaryotic immune systems has allowed for precision in correcting various disease mutations. Furthermore, delivery of genetic payloads by employing viral tropism has become a crucial and effective mechanism for delivering genes and gene editing systems into cells...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29129572/biocompatible-fluorinated-poly-%C3%AE-amino-ester-s-for-safe-and-efficient-gene-therapy
#15
Jia-Hui Gong, Yi Wang, Lei Xing, Peng-Fei Cui, Jian-Bin Qiao, Yu-Jing He, Hu-Lin Jiang
Cationic polymers have been widely used as one of the most promising non-viral vehicles for gene delivery due to their potential safety and ease of large-scale production. Here, we report the design and synthesis of a series of novel biodegradable fluorinated poly(β-amino ester)s (FPBAEs) by simple Michael-addition reaction as safe and efficient gene carrier. The results of transfection efficacy assay demonstrated the optimal FPBAE could mediated much higher GFP expression than the commercial transfection agents, polyethyleneimine (PEI, Mw = 25K) and Lipo 2000, as well as the non-fluorinated poly(β-amino ester)s (PBAE) on both HeLa and HEK-293T cell lines (higher than 70 and 90%, respectively), which was largely attributed to fluorination...
November 10, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29129531/the-diversity-structure-and-function-of-heritable-adaptive-immunity-sequences-in-the-aedes-aegypti-genome
#16
Zachary J Whitfield, Patrick T Dolan, Mark Kunitomi, Michel Tassetto, Matthew G Seetin, Steve Oh, Cheryl Heiner, Ellen Paxinos, Raul Andino
The Aedes aegypti mosquito transmits arboviruses, including dengue, chikungunya, and Zika virus. Understanding the mechanisms underlying mosquito immunity could provide new tools to control arbovirus spread. Insects exploit two different RNAi pathways to combat viral and transposon infection: short interfering RNAs (siRNAs) and PIWI-interacting RNAs (piRNAs) [1, 2]. Endogenous viral elements (EVEs) are sequences from non-retroviral viruses that are inserted into the mosquito genome and can act as templates for the production of piRNAs [3, 4]...
November 2, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/29128377/viral-hemorrhagic-fever-in-the-tropics-report-from-the-task-force-on-tropical-diseases-by-the-world-federation-of-societies-of-intensive-and-critical-care-medicine
#17
REVIEW
Jorge Luis Hidalgo Marroquin, Guy A Richards, Juan Ignacio Silesky Jiménez, Tim Baker, Pravin Amin
Viral hemorrhagic fevers (VHFs) are a group of illnesses caused by four families of viruses namely Arenaviruses, Filoviruses, Bunyaviruses, and Flaviviruses. Humans are not the natural reservoir for any of these organisms and acquire the disease through vectors from animal reservoirs. In some conditions human to human transmission is possible increasing the risk to healthy individuals in the vicinity, more so to Health Care Workers (HCW). The pathogenesis of VHF, though poorly understood, varies according to the viruses involved...
November 4, 2017: Journal of Critical Care
https://www.readbyqxmd.com/read/29127625/gene-therapy-for-hemophilia-progress-to-date
#18
John C Chapin, Paul Edward Monahan
Hemophilia is a congenital bleeding disorder that affects nearly half a million individuals worldwide. Joint bleeding and other co-morbidities are a significant source of debilitation for this population. Current therapies are effective but must be given lifelong at regular intervals, are costly, and are available to only about 25% of the hemophilia population living in resource-rich countries. Gene therapy for hemophilia has been in development for three decades and is now entering pivotal-stage clinical trials...
November 10, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/29125860/autophagy-pathway-induced-by-a-plant-virus-facilitates-viral-spread-and-transmission-by-its-insect-vector
#19
Yong Chen, Qian Chen, Manman Li, Qianzhuo Mao, Hongyan Chen, Wei Wu, Dongsheng Jia, Taiyun Wei
Many viral pathogens are persistently transmitted by insect vectors and cause agricultural or health problems. Generally, an insect vector can use autophagy as an intrinsic antiviral defense mechanism against viral infection. Whether viruses can evolve to exploit autophagy to promote their transmission by insect vectors is still unknown. Here, we show that the autophagic process is triggered by the persistent replication of a plant reovirus, rice gall dwarf virus (RGDV) in cultured leafhopper vector cells and in intact insects, as demonstrated by the appearance of obvious virus-containing double-membrane autophagosomes, conversion of ATG8-I to ATG8-II and increased level of autophagic flux...
November 10, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29125649/milker-s-nodule-an-occupational-infection-and-threat-to-the-immunocompromised
#20
REVIEW
Nancy S Handler, M Z Handler, Andris Rubins, Silvestr Rubins, Marcis Septe, Camila K Janniger, Robert A Schwartz
Milker's nodule virus, also called paravaccinia virus is a DNA virus of the parapoxvirus genus transmitted from infected cows to humans. It results from contact with cattle, cattle byproducts, or fomites. Classified as an occupational disorder, those at risk of exposure include farmers, butchers, and agricultural tourists. The viral infection begins 5-15 days after inoculation as an erythematous-purple, round nodule with a clear depressed center, and a surrounding erythematous ring. While familiar to those in farming communities, the presence of the nodule may be concerning to others, particularly the immunosuppressed...
November 10, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
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