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https://www.readbyqxmd.com/read/28532005/non-viral-strategies-for-ocular-gene-delivery
#1
REVIEW
Ana V Oliveira, Ana M Rosa da Costa, Gabriela A Silva
The success of gene therapy relies on efficient gene transfer and stable transgene expression. The in vivo efficiency is determined by the delivery vector, route of administration, therapeutic gene, and target cells. While some requirements are common to several strategies, others depend on the target disease and transgene product. Consequently, it is unlikely that a single system is suitable for all applications. This review examines current gene therapy strategies, focusing on non-viral approaches and the use of natural polymers with the eye, and particularly the retina, as their gene delivery target...
August 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28531165/a-japanese-encephalitis-virus-vaccine-inducing-antibodies-strongly-enhancing-in-vitro-infection-is-protective-in-pigs
#2
Obdulio García-Nicolás, Meret E Ricklin, Matthias Liniger, Nathalie J Vielle, Sylvie Python, Philippe Souque, Pierre Charneau, Artur Summerfield
The Japanese encephalitis virus (JEV) is responsible for zoonotic severe viral encephalitis transmitted by Culex mosquitoes. Although birds are reservoirs, pigs play a role as amplifying hosts, and are affected in particular through reproductive failure. Here, we show that a lentiviral JEV vector, expressing JEV prM and E proteins (TRIP/JEV.prME), but not JEV infection induces strong antibody-dependent enhancement (ADE) activities for infection of macrophages. Such antibodies strongly promoted infection via Fc receptors...
May 22, 2017: Viruses
https://www.readbyqxmd.com/read/28530135/prolonged-expression-of-secreted-enzymes-in-dogs-after-liver-directed-delivery-of-i-sleeping-beauty-i-transposons-implications-for-non-viral-gene-therapy-of-systemic-disease
#3
Elena L Aronovich, Kendra Anne Hyland, Bryan C Hall, Jason B Bell, Erik R Olson, Myra Urness Rusten, David W Hunter, N Matthew Ellinwood, R Scott McIvor, Perry B Hackett
The non-viral, integrating Sleeping Beauty (SB) transposon system is efficient in treating systemic monogenic disease in mice including hemophilias A and B caused by deficiency of blood clotting factors and mucopolysaccharidosis (MPS) types I and VII caused by α-L-iduronidase (IDUA) and β-glucuronidase (GUSB) deficiency, respectively. We recently reported modified approaches of the hydrodynamics-based procedure to deliver transposons to the liver in dogs. Using the transgenic canine reporter secreted alkaline phosphatase (cSEAP), we demonstrated transgenic protein in the plasma for up to six weeks post-infusion...
May 20, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28530128/in-vivo-endocrine-secretion-of-prostacyclin-following-expression-of-a-cox-1-pgis-fusion-protein-in-the-salivary-glands-of-rats-via-non-viral-gene-therapy
#4
Zhimin Wang, Raymond L Benza, Lee Zourelias, Angela Sanguino, Ramaz Geguchadze, Kelly J Shields, Changgong Wu, Kristin B Highland, Michael J Passineau
Pulmonary arterial hypertension is a progressive disease that culminates in right heart failure and death. Prostacyclin(PGI2) and its derivatives are effective treatments for PAH when administered as continuous parenteral infusions. This treatment paradigm requires medical sophistication, and patients are at risk for complications from an indewelling catheter; drug interruptions may result in rebound pulmonary hypertension and death. We hypothesized that the salivary gland can be repurposed into an endogenous production site for circulating PGI2 through the expression of a fusion protein embodying cyclooxygenase-1(Cox1) and prostacyclin synthase(PGIS) domains...
May 20, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28527117/non-viral-and-viral-delivery-systems-for-crispr-cas9-technology-in-the-biomedical-field
#5
REVIEW
Zhi-Yao He, Ke Men, Zhou Qin, Yang Yang, Ting Xu, Yu-Quan Wei
The clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR-Cas9) system provides a novel genome editing technology that can precisely target a genomic site to disrupt or repair a specific gene. Some CRISPR-Cas9 systems from different bacteria or artificial variants have been discovered or constructed by biologists, and Cas9 nucleases and single guide RNAs (sgRNA) are the major components of the CRISPR-Cas9 system. These Cas9 systems have been extensively applied for identifying therapeutic targets, identifying gene functions, generating animal models, and developing gene therapies...
May 2, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28524912/gold-nanocages-with-dual-modality-for-image-guided-therapeutics
#6
Shijin Bao, Shengnan Huang, Ying Liu, Yurong Hu, Weiping Wang, Mengfei Ji, Huili Li, Ning Xia Zhang, Chengzhi Song, Shaofeng Duan
Numerous studies have demonstrated that microRNAs are very important in cancer development and progression. However, the complex relationship between the size of microRNA delivery systems, cellular uptake, biodistribution and therapeutic efficiency remains unclear. Herein, we have successfully constructed a series of differently-sized microRNA delivery systems, miR-26a-loaded, hyaluronic acid-modified, polyetherimide-conjugated PEGylated gold nanocage ternary nanocomplexes (PPHAuNCs-TNCs), which can be monitored optically by fluorescence and photoacoustic tomography imaging...
May 19, 2017: Nanoscale
https://www.readbyqxmd.com/read/28514450/evolutionary-enhancement-of-zika-virus-infectivity-in-aedes-aegypti-mosquitoes
#7
Yang Liu, Jianying Liu, Senyan Du, Chao Shan, Kaixiao Nie, Rudian Zhang, Xiao-Feng Li, Renli Zhang, Tao Wang, Cheng-Feng Qin, Penghua Wang, Pei-Yong Shi, Gong Cheng
Zika virus (ZIKV) remained obscure until the recent explosive outbreaks in French Polynesia (2013-2014) and South America (2015-2016). Phylogenetic studies have shown that ZIKV has evolved into African and Asian lineages. The Asian lineage of ZIKV was responsible for the recent epidemics in the Americas. However, the underlying mechanisms through which ZIKV rapidly and explosively spread from Asia to the Americas are unclear. Non-structural protein 1 (NS1) facilitates flavivirus acquisition by mosquitoes from an infected mammalian host and subsequently enhances viral prevalence in mosquitoes...
May 17, 2017: Nature
https://www.readbyqxmd.com/read/28513659/serum-resistant-reactive-oxygen-species-ros-potentiated-gene-delivery-in-cancer-cells-mediated-by-fluorinated-diselenide-crosslinked-polyplexes
#8
Qiurong Deng, Xudong Li, Lipeng Zhu, Hua He, Donglai Chen, Yongbing Chen, Lichen Yin
The transfection performance of polycations is often hampered by various systemic barriers that pose conflicting requirements for material design. Herein, we developed fluorinated, ROS-cleavable polyethylenimine (PEI) for effective and serum-resistant gene delivery to cancer cells, by harmonizing the inconsistency between DNA condensation and release, and the inconsistency between cellular internalization and serum stability. Low-molecular weight (MW) PEI was cross-linked with a diselenide-containing linker and further modified with fluorocarbon chains...
May 17, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28508949/zn-ii-dipicolylamine-based-metallo-lipids-as-novel-non-viral-gene-vectors
#9
Rong-Chuan Su, Qiang Liu, Wen-Jing Yi, Zhi-Gang Zhao
In this study, a series of Zn(II)-dipicolylamine (Zn-DPA) based cationic lipids bearing different hydrophobic tails (long chains, α-tocopherol, cholesterol or diosgenin) were synthesized. Structure-activity relationship (SAR) of these lipids was studied in detail by investigating the effects of several structural aspects including the type of hydrophobic tails, the chain length and saturation degree. In addition, several assays were used to study their interactions with plasmid DNA, and results reveal that these lipids could condense DNA into nanosized particles with appropriate size and zeta-potentials...
May 16, 2017: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/28506310/unexpected-evolutionarily-conserved-rapid-effects-of-viral-infection-on-oxytocin-receptor-and-tgf-%C3%AE-psmad3
#10
Yutong Liu, Irina Conboy
BACKGROUND: shRNA lentiviral vectors are extensively used for gene knockdowns in mammalian cells, and non-target shRNAs typically are considered the proper experimental control for general changes caused by RNAi. However, the effects of non-target lentivirus controls on the modulation of cell signaling pathways remain largely unknown. In this study, we evaluated the effect of control lentiviral transduction on oxytocin receptor (OXTR) expression through the ERK/MAPK pathway in mouse and human skeletal muscle cells, on myogenic activity, and in vivo on mouse muscle regeneration...
May 15, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28497073/integrase-deficient-lentiviral-vector-as-an-all-in-one-platform-for-highly-efficient-crispr-cas9-mediated-gene-editing
#11
Pavel I Ortinski, Bernadette O'Donovan, Xiaoyu Dong, Boris Kantor
The CRISPR/Cas9 systems have revolutionized the field of genome editing by providing unprecedented control over gene sequences and gene expression in many species, including humans. Lentiviral vectors (LVs) are one of the primary delivery platforms for the CRISPR/Cas9 system due to their ability to accommodate large DNA payloads and sustain robust expression in a wide range of dividing and non-dividing cells. However, long-term expression of LV-delivered Cas9/guide RNA may lead to undesirable off-target effects characterized by non-specific RNA-DNA interactions and off-target DNA cleavages...
June 16, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28494741/delivering-sirna-with-dendrimers-in-vivo-applications
#12
Victoria Leiro, Sofia Duque Santos, Ana Paula Pêgo
Over the last decades, gene therapy has emerged as a pioneering therapeutic approach to treat or prevent several diseases. Among the explored strategies, the short-term silencing of protein coding genes mediated by siRNAs has a good therapeutic potential in a clinical setting. However, the widespread use of siRNA will require the development of clinically suitable, safe and effective vehicles with the ability to complex and deliver siRNA into target cells with minimal toxicity. Lately, dendrimers have gained considerable attention as non-viral vectors in nucleic acid delivery due to their unique structural characteristics (globular, well defined and highly branched structure, multivalency, low polydispersity and tunable nanosize), along with their relevant capacity to complex and protect nucleic acids in compact nanostructures, which can be functionalized with targeting moieties in order to get cell specificity...
May 10, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/28494195/functionally-inactivated-dominant-viral-antigens-of-human-cytomegalovirus-delivered-in-replication-incompetent-adenovirus-type-6-vectors-as-vaccine-candidates
#13
Aimin Tang, Daniel C Freed, Fengsheng Li, Steve Meschino, Michael Prokop, Andrew Bett, Danilo Casimiro, Dai Wang, Tong-Ming Fu
T cell immunity is critical in controlling human cytomegalovirus (HCMV) infection in transplant recipients, and T cells targeting viral immediate early proteins such as IE1, IE2 and pp65 have been speculated to be more effective against reactivation. Here we report efforts to construct replication incompetent adenovirus 6 vectors expressing these viral antigens as vaccine candidates. To reduce the potential liabilities of these viral proteins as vaccine antigens, we introduced mutations to inactivate their reported functions including their nuclear localization signals...
May 11, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28487936/protein-therapy-using-mafa-fused-to-a-polyarginine-transduction-domain-attenuates-glucose-levels-of-streptozotocin%C3%A2-induced-diabetic-mice
#14
Jun Lu, Lingjing Lin, Huiyue Dong, Xin Meng, Fang Fang, Qinghua Wang, Lianghu Huang, Jianming Tan
Ectopic expression of musculo aponeurotic fibrosarcoma BZIP transcription factor (Maf) A, has previously been demonstrated to induce insulin expression in non‑β‑cell lines. Protein transduction domains acting as an alternative delivery strategy may deliver heterogeneous proteins into cells. A sequence of 11 arginine residues (11R) has been demonstrated to act as a particularly efficient vector to introduce proteins into various cell types. The present study constructed 11R‑fused MafA to achieve transduction of the protein into cellular membranes and subsequently examined the therapeutic effect of the MafA‑11R protein in streptozotocin‑induced diabetes...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28487469/phosphoinositide-3-kinase-p110%C3%AE-gene-delivery-limits-diabetes-induced-cardiac-nadph-oxidase-and-cardiomyopathy-in-a-mouse-model-with-established-diastolic-dysfunction
#15
Darnel Prakoso, Miles J DeBlasio, Chengxue Qin, Sarah Rosli, Helen Kiriazis, Hongwei Qian, Xiao-Jun Du, Kate L Weeks, Paul Gregorevic, Julie R McMullen, Rebecca H Ritchie
Phosphoinositide 3-kinase [PI3K (p110α)] is able to negatively regulate the diabetes-induced increase in NADPH oxidase in the heart. Patients affected by diabetes exhibit significant cardiovascular morbidity and mortality, at least in part due to a cardiomyopathy characterised by oxidative stress and left ventricular (LV) dysfunction. Thus, PI3K (p110α) may represent a novel approach to protect the heart from diabetes-induced cardiac oxidative stress and dysfunction. In the current study, we investigated the therapeutic potential of a delayed intervention with cardiac-targeted PI3K gene therapy, administered to mice with established diabetes-induced LV diastolic dysfunction...
May 9, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28482114/innovations-in-gene-and-growth-factor-delivery-systems-for-diabetic-wound-healing
#16
REVIEW
Ashang Luwang Laiva, Fergal J O'Brien, Michael B Keogh
The rise in lower extremity amputations (LEAs) due to non-healing of foot ulcers in diabetic patients calls for rapid improvement in effective treatment regimens. Administration of growth factors (GFs) are thought to offer an off-the-shelf treatment however, the dose- and time-dependent efficacy of the GFs together with the hostile environment of diabetic wound beds impose a major hindrance in the selection of an ideal route for GFs delivery. As an alternative, the delivery of therapeutic genes using viral and non-viral vectors, capable of transiently expressing the genes until the recovery of the wounded tissue offers promise...
May 8, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28476586/manipulating-the-membrane-penetration-mechanism-of-helical-polypeptides-via-aromatic-modification-for-efficient-gene-delivery
#17
Nan Zheng, Ziyuan Song, Jiandong Yang, Yang Liu, Fangfang Li, Jianjun Cheng, Lichen Yin
The delivery performance of non-viral gene vectors is greatly related to their intracellular kinetics. Cationic helical polypeptides with potent membrane penetration properties and gene transfection efficiencies have been recently developed by us. However, they suffer from severe drawbacks in terms of their membrane penetration mechanisms that mainly include endocytosis and pore formation. The endocytosis mechanism leads to endosomal entrapment of gene cargos, while the charge- and helicity-induced pore formation causes appreciable cytotoxicity at high concentrations...
May 2, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28473703/engineered-hsv-vector-achieves-safe-long-term-transgene-expression-in-the-central-nervous-system
#18
Gianluca Verlengia, Yoshitaka Miyagawa, Selene Ingusci, Justus B Cohen, Michele Simonato, Joseph C Glorioso
Previously we reported a new series of highly defective herpes simplex virus type 1 (HSV-1) vectors that were functionally devoid of all viral immediately early (IE) genes, resulting in virtual absence of viral gene expression. Nevertheless, a reporter gene cassette inserted into the vector flanked by boundary elements from the viral latency locus showed high, persistent reporter gene activity in non-neuronal cells while an independent expression cassette inserted into a deleted ICP4 locus remained almost silent...
May 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28471518/bacterial-microbiota-in-small-brown-planthopper-populations-with-different-rice-viruses
#19
Shuo Li, Changwei Zhou, Guangyi Chen, Yijun Zhou
The small brown planthopper (SBPH) is an important virus vector, transmitting Rice stripe virus (RSV), and Rice black-streaked dwarf virus (RBSDV). Insect symbionts play an essential role in the insect fitness, however, it is still unclear about their contributions to viral transmission by SBPH. Here, we investigated endosymbiont communities in non-viruliferous, RSV-infected, and RBSDV-infected SBPH populations using Illumina 16S rRNA gene MiSeq sequencing. In total, 281,803 effective sequences of the 16S rRNA gene were generated from different samples...
May 4, 2017: Journal of Basic Microbiology
https://www.readbyqxmd.com/read/28468883/cxcl10-cxcr3-dependent-mobilization-of-hsv-specific-cd8-tem-and-cd8-trm-cells-within-infected-tissues-allows-efficient-protection-against-recurrent-herpes-infection-and-disease
#20
Ruchi Srivastava, Arif A Khan, Sravya Chilukuri, Sabrina A Syed, Tien T Tran, Julie Furness, Elmostafa Bahraoui, Lbachir BenMohamed
Herpes simplex virus type 1 (HSV-1) establishes latency within the sensory neurons of the trigeminal ganglia (TG). HSV-specific memory CD8(+) T cells play a critical role in preventing HSV-1 reactivation from TG and subsequent virus shedding in tears that trigger recurrent corneal herpetic disease. The CXCL10/CXCR3 chemokine pathway promotes T cell immunity to many viral pathogens, but its importance in CD8(+) T cell immunity to recurrent herpes has been poorly elucidated. In this study, we determined how the CXCL10/CXCR3 pathway affects TG- and cornea-resident CD8(+) T cell responses to recurrent ocular herpes infection and disease using a well-established murine model in which HSV-1 reactivation was induced from latently infected TG by UV-B light...
May 3, 2017: Journal of Virology
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