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https://www.readbyqxmd.com/read/28821028/targeted-gene-delivery-of-polyethyleneimine-grafted-chitosan-with-rgd-dendrimer-peptide-in-%C3%AE-v%C3%AE-3-integrin-overexpressing-tumor-cells
#1
Young-Min Kim, Seong-Cheol Park, Mi-Kyeong Jang
The safe and effective delivery of genetic material into cells is a necessary factor for gene therapy. Although a wide range of materials, methods, and combinations have been reported, successful gene therapy has been limited. In the present study, a targeted gene carrier for αvβ3 integrin-overexpressing tumor cells was designed using widely applied materials containing water soluble chitosan (WSC), RGD peptide, and polyethyleneimine (PEI). The physiological characteristics, in vitro targeted gene transfection, cytotoxicity, blood-compatibility, and cellular distributions were investigated...
October 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28820183/technique-of-retinal-gene-therapy-delivery-of-viral-vector-into-the-subretinal-space
#2
K Xue, M Groppe, A P Salvetti, R E MacLaren
PurposeSafe and reproducible delivery of gene therapy vector into the subretinal space is essential for successful targeting of the retinal pigment epithelium (RPE) and photoreceptors. The success of surgery is critical for the clinical efficacy of retinal gene therapy. Iatrogenic detachment of the degenerate (often adherent) retina in patients with hereditary retinal degenerations and small volume (eg, 0.1 ml) subretinal injections pose new surgical challenges.MethodsOur subretinal gene therapy technique involved pre-operative planning with optical coherence tomography (OCT) and autofluorescence (AF) imaging, 23 G pars plana vitrectomy, internal limiting membrane staining with Membrane Blue Dual (DORC BV, Zuidland, Netherlands), a two-step subretinal injection using a 41 G Teflon tipped cannula (DORC) first with normal saline to create a parafoveal bleb followed by slow infusion of viral vector via the same self-sealing retinotomy...
August 18, 2017: Eye
https://www.readbyqxmd.com/read/28820072/structural-design-and-physicochemical-foundations-of-hydrogels-for-biomedical-and-pharmaceutical-applications
#3
Qingyong Li, Wen Li, Jie Xu, Zhengxiang Ning, Jiaoyan Ren, Wenzhen Liao
Biomedical research, known as medical research, is conducive to support and promote the development of knowledge in the field of medicine. Hydrogels have been extensively used in many biomedical fields due to theirs highly absorbent and flexible properties. The smart hydrogels, especially, can respond to a broad range of external stimuli such as temperature, pH value, light, electric and magnetic fields. With excellent biocompatibility, tunable rheology, mechanical properties, porosity, and hydrated molecular structure, hydrogels are considered as promising candidate for simulating local tissue microenvironment...
August 17, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28818675/presence-of-quintuple-dhfr-n51-c59-s108-dhps-a437-k540-mutations-in-plasmodium-falciparum-isolates-from-pregnant-women-and-the-general-population-in-nanoro-burkina-faso
#4
Esmée Ruizendaal, Marc C Tahita, Maminata Traoré, Halidou Tinto, Henk D F H Schallig, Petra F Mens
Sulphadoxine-pyrimethamine (SP) is only used for intermittent preventive treatment during pregnancy (IPTp) in most Sub-Saharan African countries. However, there are concerns about the efficacy of IPTp-SP because of increasing resistance. Combinations of point mutations in the dhps and dhfr genes of Plasmodium falciparum are associated with SP resistance, in particular the quintuple dhfr (N51, C59, S108) - dhps (codons A437, K540) mutant. In Nanoro, Burkina Faso, filter paper samples from pregnant women at first antenatal care visit and at delivery plus samples from the general population (GP) were studied for dhfr and dhps mutations by sequencing...
August 14, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28817973/the-agma1-polyamidoamine-mediates-the-efficient-delivery-of-sirna
#5
Roberta Cavalli, Luca Primo, Roberto Sessa, Giulia Chiaverina, Laura di Blasio, Jenny Alongi, Amedea Manfredi, Elisabetta Ranucci, Paolo Ferruti
AGMA1, a prevailingly cationic, guanidine-bearing, linear, amphoteric polyamidoamine is an effective siRNA condensing agent. Here two AGMA1 samples of different molecular weight, i.e. AGMA1-5 and AGMA1-10 were evaluated as siRNA condensing agents and transfection promoters. AGMA1-10 formed stable polyplexes with a size lower than 50 nm and positive zeta potential. AGMA1-5 polyplexes were larger, about 100 nm in size. AGMA1-10 polyplexes, but not AGMA1-5 proved to be an effective intracellular siRNA carrier, able to trigger gene silencing in Hela and PC3 cell lines without eliciting cytotoxic effects...
August 18, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28817344/a-guide-to-approaching-regulatory-considerations-for-lentiviral-mediated-gene-therapies
#6
Michael White, Roger Whittaker, Carolina Gándara, Elizabeth A Stoll
Lentiviral vectors are increasingly the gene transfer tool of choice for gene or cell therapies, with multiple clinical investigations showing promise for this viral vector in terms of both safety and efficacy. The third-generation vector system is well characterized, effectively delivers genetic material and maintains long-term stable expression in target cells, delivers larger amounts of genetic material than other methods, is nonpathogenic, and does not cause an inflammatory response in the recipient. This report aims to help academic scientists and regulatory managers negotiate the governance framework to achieve successful translation of a lentiviral vector-based gene therapy...
August 2017: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/28817343/suppression-of-choroidal-neovascularization-in-mice-by-subretinal-delivery-of-multigenic-lentiviral-vectors-encoding-anti-angiogenic-micrornas
#7
Anne Louise Askou, Josephine Natalia Esther Benckendorff, Andreas Holmgaard, Tina Storm, Lars Aagaard, Toke Bek, Jacob Giehm Mikkelsen, Thomas Juhl Corydon
Lentivirus-based vectors have been used for the development of potent gene therapies. Here, application of a multigenic lentiviral vector (LV) producing multiple anti-angiogenic microRNAs following subretinal delivery in a laser-induced choroidal neovascularization (CNV) mouse model is presented. This versatile LV, carrying back-to-back RNApolII-driven expression cassettes, enables combined expression of microRNAs targeting vascular endothelial growth factor A (Vegfa) mRNA and fluorescent reporters. In addition, by including a vitelliform macular dystrophy 2 (VMD2) promoter, expression of microRNAs is restricted to the retinal pigment epithelial (RPE) cells...
August 2017: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/28816060/the-broad-spectrum-antimicrobial-potential-of-mn-co-4-s2cnme-ch2co2h-a-water-soluble-co-releasing-molecule-corm-401-intracellular-accumulation-transcriptomic-and-statistical-analyses-and-membrane-polarization
#8
Lauren Katie Wareham, Samantha McLean, Ronald Begg, Namrata Rana, Salar Ali, John J Kendall, Guido Sanguinetti, Brian E Mann, Robert K Poole
AIMS: Carbon monoxide (CO)-releasing molecules (CORMs) are candidates for animal and antimicrobial therapeutics. We aimed to probe the antimicrobial potential of a novel manganese CORM. RESULTS: [Mn(CO)4S2CNMe(CH2CO2H)], CORM-401, inhibits growth of Escherichia coli and several antibiotic-resistant clinical pathogens. CORM-401 releases CO that binds oxidases in vivo but is an ineffective respiratory inhibitor. Extensive CORM accumulation (assayed as intracellular manganese) accompanies antimicrobial activity...
August 17, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28815500/nanoparticle-mediated-recombinase-delivery-into-maize
#9
Susana Martin-Ortigosa, Brian G Trewyn, Kan Wang
We describe a non-DNA-based system for delivering Cre recombinase protein into maize tissue using gold-plated mesoporous silica nanoparticle (Au-MSN). Cre protein is first loaded into the pores of Au-MSNs and then delivered using the biolistic method to immature embryos of a maize line (Lox-corn), which harbors loxP sites flanking a selection and a reporter gene. The release of the Cre recombinase protein inside the plant cell leads to recombination at the loxP sites, eliminating both genes. Visual screening is used to identify recombination events, which can be regenerated to mature and fertile plants...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28815499/marker-removal-in-transgenic-plants-using-cre-recombinase-delivered-with-potato-virus-x
#10
Lilya Kopertekh, Joachim Schiemann
In this chapter we present an alternative method to develop marker-free transgenic plants. It makes use of the Cre/loxP recombination system from bacteriophage P1 and consists of two essential components. The first component is the transgenic plant containing a loxP-flanked marker gene. The second component is a cre transient expression vector based on potato virus X. The great benefit of this transient delivery method consists in the avoidance of stable integration of the cre recombinase gene into the plant genome...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28815497/viral-delivery-of-gfp-dependent-recombinases-to-the-mouse-brain
#11
Jonathan C Y Tang, Stephanie Rudolph, Constance L Cepko
Many genetic tools have been developed that use green fluorescent protein (GFP) and its derivatives for labeling specific cell populations in organisms and in cell culture. To extend the use of GFP beyond labeling purposes, we developed methods and reagents that use GFP as a driver of biological activities. We used nanobodies that bind GFP to engineer CRE-DOG and Flp-DOG, recombinases that can induce Cre/lox and Flp/FRT recombination in a GFP-dependent manner, respectively. Here, we present a protocol to deliver CRE-DOG and Flp-DOG into the mouse brain by recombinant AAV infection...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28815492/building-cre-knockin-rat-lines-using-crispr-cas9
#12
Yuanwu Ma, Lianfeng Zhang, Xingxu Huang
Conditional gene inactivation strategy helps researchers to study the gene functions that are critical in embryogenesis or in defined tissues of adulthood. The Cre/loxP system is widely used for conditional gene inactivation/activation in cells or organisms. Cre knockin animal lines are essential for gene expression or inactivation in a spatially and temporally restricted manner. However, to generate a Cre knockin line by traditional approach is laborious. Recently, the clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9) has been proven as a simple and efficient genome-editing tool...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28815481/gene-delivery-approaches-for-mesenchymal-stem-cell-therapy-strategies-to-increase-efficiency-and-specificity
#13
REVIEW
Gopi Suresh Oggu, Shyama Sasikumar, Nirosha Reddy, Kranthi Kiran Reddy Ella, Ch Mohan Rao, Kiran Kumar Bokara
A significant number of clinical trials have been undertaken to explore the use of mesenchymal stem cells (MSCs) for the treatment of several diseases such as Crohn's disease, diabetes, bone defects, myocardial infarction, stroke etc., Due to their efficiency in homing to the tissue injury sites, their differentiation potential, the capability to secrete a large amount of trophic factors and their immunomodulatory effects, MSCs are becoming increasingly popular and expected to be one of the promising therapeutic approaches...
August 16, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28815373/autologous-nasal-chondrocytes-delivered-by-injectable-hydrogel-for-in-vivo-articular-cartilage-regeneration
#14
Wenliang Chen, Changhua Li, Maoxiu Peng, Bingju Xie, Lei Zhang, Xiaojun Tang
Cell based tissue engineering serves as a promising strategy for articular cartilage repair, which remains a challenge both for researchers and clinicians. The aim of this research was to assess the potential of autologous nasal chondrocytes (NCs) combined with alginate hydrogel as injectable constructs for rabbit articular cartilage repair. Autologous nasal chondrocytes were isolated from rabbit nasal septum, expanded either on monolayer or in 3D alginate hydrogel. In vitro, DNA quantification revealed that NCs can proliferate stable in 3D alginate matrix, but slower than that cultured in monolayer...
August 16, 2017: Cell and Tissue Banking
https://www.readbyqxmd.com/read/28815315/emerging-gene-therapies-for-genetic-hearing-loss
#15
REVIEW
Hena Ahmed, Olga Shubina-Oleinik, Jeffrey R Holt
Gene therapy, or the treatment of human disease using genetic material, for inner ear dysfunction is coming of age. Recent progress in developing gene therapy treatments for genetic hearing loss has demonstrated tantalizing proof-of-principle in animal models. While successful translation of this progress into treatments for humans awaits, there is growing interest from patients, scientists, clinicians, and industry. Nonetheless, it is clear that a number of hurdles remain, and expectations for total restoration of auditory function should remain tempered until these challenges have been overcome...
August 16, 2017: Journal of the Association for Research in Otolaryngology: JARO
https://www.readbyqxmd.com/read/28813461/epidemiology-of-clostridium-difficile-in-infants-in-oxfordshire-uk-risk-factors-for-colonization-and-carriage-and-genetic-overlap-with-regional-c-difficile-infection-strains
#16
Nicole Stoesser, David W Eyre, T Phuong Quan, Heather Godwin, Gemma Pill, Emily Mbuvi, Alison Vaughan, David Griffiths, Jessica Martin, Warren Fawley, Kate E Dingle, Sarah Oakley, Kazimierz Wanelik, John M Finney, Melina Kachrimanidou, Catrin E Moore, Sherwood Gorbach, Thomas V Riley, Derrick W Crook, Tim E A Peto, Mark H Wilcox, A Sarah Walker
BACKGROUND: Approximately 30-40% of children <1 year of age are Clostridium difficile colonized, and may represent a reservoir for adult C. difficile infections (CDI). Risk factors for colonization with toxigenic versus non-toxigenic C. difficile strains and longitudinal acquisition dynamics in infants remain incompletely characterized. METHODS: Predominantly healthy infants (≤2 years) were recruited in Oxfordshire, UK, and provided ≥1 fecal samples. Independent risk factors for toxigenic/non-toxigenic C...
2017: PloS One
https://www.readbyqxmd.com/read/28813171/anti-edar-agonist-antibody-therapy-resolves-palate-defects-in-pax9-mice
#17
S Jia, J Zhou, Y Wee, M L Mikkola, P Schneider, R N D'Souza
To date, surgical interventions are the only means by which craniofacial anomalies can be corrected so that function, esthetics, and the sense of well-being are restored in affected individuals. Unfortunately, for patients with cleft palate-one of the most common of congenital birth defects-treatment following surgery is prolonged over a lifetime and often involves multidisciplinary regimens. Hence, there is a need to understand the molecular pathways that control palatogenesis and to translate such information for the development of noninvasive therapies that can either prevent or correct cleft palates in humans...
August 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28813136/targeting-of-cellular-organelles-by-fluorescent-plasmid-dna-nanoparticles
#18
Diana Costa, Carolina Costa, Margarida Vaz Caldeira, Luisa Maria Cortes, João A Queiroz, Carla Cruz
The development of a suitable delivery system and the targeting of intracellular organelles are both essential for the success of drug and gene therapies. The conception of fluorescent ligands, displaying targeting specificity together with low toxicity, is an emerging and reliable tool to develop innovative delivery systems. Biocompatible BSA or pDNA/ligand nanoparticles were synthesized by a co-precipitation method and were shown to display adequate sizes and morphology for delivery purposes, and positive surface charges...
August 16, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28810808/advances-and-challenges-in-cardiovascular-gene-therapy
#19
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/28810532/plga-ctab-curcumin-nanoparticles-fabrication-characterization-and-molecular-basis-of-anticancer-activity-in-triple-negative-breast-cancer-cell-lines-mda-mb-231-cells
#20
Ramovatar Meena, Sumit Kumar, Raj Kumar, Usha Singh Gaharwar, Paulraj Rajamani
Triple-negative breast cancers (TNBC) are aggressive cancers, which do not control by hormonal therapy or therapies that target HER-2 receptors. Curcumin (Cur) has shown cytotoxic effects in multiple cancer cell lines. However, its medical uses remain limited due to low aqueous solubility and poor bioavailability. Therefore, present study was aimed to fabricate the small positive charge curcumin nanoparticles (CN) by nanoprecipitation methods using PLGA and CTAB, and to evaluate its anticancer efficacy and underlying the mechanism in triple negative breast cancer cell lines (MDA-MB-231 cells)...
August 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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