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https://www.readbyqxmd.com/read/28651005/optimization-of-a-murine-and-human-tissue-model-to-recapitulate-dermal-and-pulmonary-features-of-systemic-sclerosis
#1
Tomoya Watanabe, Tetsuya Nishimoto, Logan Mlakar, Jonathan Heywood, Maya Malaab, Stanley Hoffman, Carol Feghali-Bostwick
The murine bleomycin (BLM)-induced fibrosis model is the most widely used in systemic sclerosis (SSc) studies. It has been reported that systemic delivery of BLM via continuous diffusion from subcutaneously implanted osmotic minipumps can cause fibrosis of the skin, lungs, and other internal organs. However, the mouse strain, dosage of BLM, administration period, and additional important features differ from one report to the next. In this study, by employing the pump model in C57BL/6J mice, we show a dose-dependent increase in lung fibrosis by day 28 and a transient increase in dermal thickness...
2017: PloS One
https://www.readbyqxmd.com/read/28650965/epigenetic-adaptation-of-the-placental-serotonin-transporter-gene-slc6a4-to-gestational-diabetes-mellitus
#2
Sofia Blazevic, Marina Horvaticek, Maja Kesic, Peter Zill, Dubravka Hranilovic, Marina Ivanisevic, Gernot Desoye, Jasminka Stefulj
We tested the hypothesis that gestational diabetes mellitus (GDM) alters the DNA methylation pattern of the fetal serotonin transporter gene (SLC6A4), and examined the functional relevance of DNA methylation for regulation of the SLC6A4 expression in the human placenta. The study included 50 mother-infant pairs. Eighteen mothers were diagnosed with GDM and 32 had normal glucose tolerance (NGT). All neonates were of normal birth weight and born at term by planned Cesarean section. DNA and RNA were isolated from samples of tissue collected from the fetal side of the placenta immediately after delivery...
2017: PloS One
https://www.readbyqxmd.com/read/28650460/a-calcium-and-light-gated-switch-to-induce-gene-expression-in-activated-neurons
#3
Dongmin Lee, Jung Ho Hyun, Kanghoon Jung, Patrick Hannan, Hyung-Bae Kwon
Despite recent advances in optogenetics, it remains challenging to manipulate gene expression in specific populations of neurons. We present a dual-protein switch system, Cal-Light, that translates neuronal-activity-mediated calcium signaling into gene expression in a light-dependent manner. In cultured neurons and brain slices, we show that Cal-Light drives expression of the reporter EGFP with high spatiotemporal resolution only in the presence of both blue light and calcium. Delivery of the Cal-Light components to the motor cortex of mice by viral vectors labels a subset of excitatory and inhibitory neurons related to learned lever-pressing behavior...
June 26, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28649641/multifunctional-poly-amine-co-ester-co-ortho-ester-for-efficient-and-safe-gene-delivery
#4
Junwei Zhang, Jiajia Cui, Yang Deng, Zhaozhong Jiang, W Mark Saltzman
Cationic polymers are used for non-viral gene delivery, but current materials lack the functionality to address the multiple barriers involved in gene delivery. Here we describe the rational design and synthesis of a new family of quaterpolymers with unprecedented multifunctionality: acid sensitivity, low cationic charge, high hydrophobicity, and biodegradability, all of which are essential for efficient and safe gene delivery. The polymers were synthesized via lipase-catalyzed polymerization of ortho ester diester, lactone, dialkyl diester, and amino diol monomers...
November 14, 2016: ACS Biomaterials Science & Engineering
https://www.readbyqxmd.com/read/28648139/mutagenic-analysis-of-an-adeno-associated-virus-variant-capable-of-simultaneously-promoting-immune-resistance-and-robust-gene-delivery
#5
Yoojin Kim, Eunmi Kim, Seokmin Oh, Ye-Eun Yoon, Jae-Hyung Jang
In addition to the ability to boost gene delivery efficiency in many therapeutically relevant cells, the capability of circumventing neutralizing antibody (NAb) inactivation is a key prerequisite that gene carriers must fulfill for their extensive applications as therapeutic agents in many gene therapy trials, especially for cancer treatments. This study revealed that a genetically engineered adeno-associated viral (AAV) variant, AAVr3.45, inherently possesses dual beneficial properties as a gene carrier: i) efficiently delivering therapeutic genes to many clinically valuable cells (e...
June 24, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28647733/role-of-mesenchymal-stem-cells-in-bone-regenerative-medicine-what-is-the-evidence
#6
Ahmad Oryan, Amir Kamali, Ali Moshiri, Mohamadreza Baghaban Eslaminejad
Healing and regeneration of bone injuries, particularly those that are associated with large bone defects, are a complicated process. There is growing interest in the application of osteoinductive and osteogenic growth factors and mesenchymal stem cells (MSCs) in order to significantly improve bone repair and regeneration. MSCs are multipotent stromal stem cells that can be harvested from many different sources and differentiated into a variety of cell types, such as preosteogenic chondroblasts and osteoblasts...
June 24, 2017: Cells, Tissues, Organs
https://www.readbyqxmd.com/read/28647589/mannose-conjugated-layered-double-hydroxide-nanocomposite-for-targeted-sirna-delivery-to-enhanced-cancer-therapy
#7
Li Li, Run Zhang, Wenyi Gu, Zhi Ping Xu
Sheet-like layered double hydroxide nanoparticles (LDH NPs) have showed great potentials in biomedical applications such as nanocarriers for drug and gene delivery, biosensors and imaging agents. However, target delivery of drugs and genes using LDH NPs to the desired tumor sites is a major challenge in cancer therapy. The aim of this study is to develop a functional LDH-based nanocomposite for target delivery of siRNA to cancer cells. Mannose as a targeting moiety was firstly conjugated onto SiO2-coated LDH nanocomposite...
June 21, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28647433/targeted-release-of-transcription-factors-for-human-cell-reprogramming-by-zebra-cell-penetrating-peptide
#8
Benjamin Caulier, Lionel Berthoin, Helène Coradin, Frédéric Garban, Marie Claire Dagher, Benoît Polack, Bertrand Toussaint, Jean Luc Lenormand, David Laurin
Transcription factors (TFs) are key actors of the control of gene expression and consequently of every major process within cells, ranging from cell fate determination, cell cycle control and response to environment. Their ectopic expression has proven high potential in reprogramming cells for regenerative medicine; ontogenesis studies and cell based modelling. Direct delivery of proteins could represent an alternative to current reprogramming methods using gene transfer but still needs technological improvements...
June 21, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28647114/status-of-therapeutic-gene-transfer-to-treat-cardiovascular-disease-in-dogs-and-cats
#9
REVIEW
Meg M Sleeper
Gene therapy is a procedure resulting in the transfer of a gene into an individual's cells to treat a disease. One goal of gene transfer is to express a functional gene when the endogenous gene is inactive. However, because heart failure is a complex disease characterized by multiple abnormalities at the cellular level, an alternate gene delivery approach is to alter myocardial protein levels to improve function. This article discusses background information on gene delivery including packaging, administration, and a brief discussion of some of the candidate transgenes likely to alter the progression of naturally occurring heart disease in dogs and cats...
June 21, 2017: Veterinary Clinics of North America. Small Animal Practice
https://www.readbyqxmd.com/read/28646272/rhesus-cochlear-and-vestibular-functions-are-preserved-after-inner-ear-injection-of-saline-volume-sufficient-for-gene-therapy-delivery
#10
Chenkai Dai, Mohamed Lehar, Daniel Q Sun, Lani Swarthout Rvt, John P Carey, Tim MacLachlan, Doug Brough, Hinrich Staecker, Alexandra M Della Santina, Timothy E Hullar, Charles C Della Santina
Sensorineural losses of hearing and vestibular sensation due to hair cell dysfunction are among the most common disabilities. Recent preclinical research demonstrates that treatment of the inner ear with a variety of compounds, including gene therapy agents, may elicit regeneration and/or repair of hair cells in animals exposed to ototoxic medications or other insults to the inner ear. Delivery of gene therapy may also offer a means for treatment of hereditary hearing loss. However, injection of a fluid volume sufficient to deliver an adequate dose of a pharmacologic agent could, in theory, cause inner ear trauma that compromises functional outcome...
June 23, 2017: Journal of the Association for Research in Otolaryngology: JARO
https://www.readbyqxmd.com/read/28645658/spacer-structure-and-hydrophobicity-influences-transfection-activity-of-novel-polycationic-gemini-amphiphiles
#11
Pavel A Puchkov, Irina A Kartashova, Elena V Shmendel, Anastasya S Luneva, Nina G Morozova, Marina A Zenkova, Mikhail A Maslov
Three novel polycationic gemini amphiphiles with different spacers were developed and evaluated in terms of their physiochemical properties and transfection efficiencies. Cationic liposomes formed by these amphiphiles and the helper lipid DOPE were able to successfully condense DNA, as shown by gel mobility shift and ethidium bromide intercalation assays. Transfection activity of the liposomes was superior to Lipofectamine(®) 2000 and was dependent on spacer structure, hydrophobicity, and nucleic acid type (pDNA or siRNA)...
June 10, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28645300/bacterial-ghosts-as-adjuvants-mechanisms-and-potential
#12
REVIEW
Irshad A Hajam, Pervaiz A Dar, Gayeon Won, John Hwa Lee
Bacterial ghosts (BG) are empty cell envelopes derived from Gram-negative bacteria. They contain many innate immunostimulatory agonists, and are potent activators of a broad range of cell types involved in innate and adaptive immunity. Several considerable studies have demonstrated the effectiveness of BG as adjuvants as well as their ability to induce proinflammatory cytokine production by a range of immune and non-immune cell types. These proinflammatory cytokines trigger a generalized recruitment of T and B lymphocytes to lymph nodes that maximize the chances of encounter with their cognate antigen, and subsequent elicitation of potent immune responses...
June 24, 2017: Veterinary Research
https://www.readbyqxmd.com/read/28645240/engineered-expression-of-broadly-neutralizing-antibodies-against-human-immunodeficiency-virus
#13
Maham Ahmad, Osama M Ahmed, Bruce Schnepp, Philip R Johnson
This review discusses recent progress made in developing a vaccine and novel treatments for human immunodeficiency virus (HIV). It highlights the shortcomings of the RV144 vaccination trial [ALVAC-HIV (vCP1521) and AIDSVAX B/E] and the current standard of care and proposes that engineered expression of broadly neutralizing antibodies (bNAbs) against HIV-1 could overcome these shortcomings. Current developments in three major lines of research on HIV prevention and treatment using bNAbs are reviewed: firstly, the use of sequential immunogens to activate B cells to express bNAbs; secondly, the delivery of novel and extremely potent bNAbs through passive administration; and finally, the use of gene transfer using adeno-associated viral vectors to deliver bNAbs...
June 23, 2017: Annual Review of Virology
https://www.readbyqxmd.com/read/28645023/maternal-serum-pfoa-concentration-and-dna-methylation-in-cord-blood-a-pilot-study
#14
Samantha L Kingsley, Karl T Kelsey, Rondi Butler, Aimin Chen, Melissa N Eliot, Megan E Romano, Andres Houseman, Devin C Koestler, Bruce P Lanphear, Kimberly Yolton, Joseph M Braun
Perfluorooctanoic acid (PFOA), a perfluoroalkyl substance, is commonly detected in the serum of pregnant women and may impact fetal development via epigenetic re-programming. In a pilot study, we explored associations between serum PFOA concentrations during pregnancy and offspring peripheral leukocyte DNA methylation at delivery in women with high (n = 22, range: 12-26ng/mL) and low (n = 22, range: 1.1-3.1ng/mL) PFOA concentrations. After adjusting for cell type, child sex, and income, we did not find differences in CpG methylation in the two exposure groups that reached epigenome-wide significance...
June 20, 2017: Environmental Research
https://www.readbyqxmd.com/read/28643952/asn194lys-mutation-in-rvg29-peptide-increases-gfp-transgene-delivery-by-endocytosis-to-neuroblastoma-and-astrocyte-cells
#15
Sheila Adela Villa-Cedillo, Humberto Rodríguez-Rocha, Laura Mireya Zavala-Flores, Roberto Montes-de-Oca-Luna, Aracely García-García, Maria de Jesus Loera-Arias, Odila Saucedo-Cárdenas
OBJECTIVES: A cell-penetrating peptide-based delivery system could target specific types of cells for therapeutic genes delivery. To increase the gene delivery efficiency into neuronal phenotype cells, we introduced an Asn194Lys mutation to RVG29 peptide derived from rabies virus glycoprotein and added a nuclear localization signal to enhance its nuclear import. METHODS: Mutant RVG or wild-type RVG peptide, a karyophilic peptide (KP) and a plasmid encoding green fluorescent protein (pGL) were bound by electrostatic charges to form four different kinds of RVG complexes...
June 23, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28643325/surface-expression-of-anti-cd3scfv-stimulates-locoregional-immunotherapy-against-hepatocellular-carcinoma-depending-on-the-e1a-engineered-human-umbilical-cord-mesenchymal-stem-cells
#16
Qing Zhang, Xiang-Fei Yuan, Yang Lu, Zhen-Zhen Li, Shi-Qi Bao, Xiao-Long Zhang, Yuan-Yuan Yang, Dong-Mei Fan, Yi-Zhi Zhang, Chen-Xuan Wu, Hong-Xing Guo, Yan-Jun Zhang, Ye Zhou, Dong-Sheng Xiong
Tumor antigens is at the core of cancer immunotherapy, however, the ideal antigen selection is difficult especially in poorly immunogenic tumors. In this study, we designed a strategy to modify hepatocellular carcinoma (HCC) cells by surface expressing anti-CD3scfv within the tumor site strictly, which depended on the E1A-engineered human umbilical cord mesenchymal stem cells (HUMSC.E1A) delivery system. Subsequently, membrane-bound anti-CD3scfv actived the lymphocytes which lysed HCC cells bypassing the expression of antigens or MHC restriction...
June 23, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28642329/experimental-and-computational-insight-into-human-mesenchymal-stem-cell-paracrine-signaling-and-heterocellular-coupling-effects-on-cardiac-contractility-and-arrhythmogenicity
#17
Joshua Mayourian, Timothy J Cashman, Delaine K Ceholski, Bryce V Johnson, David Sachs, Deepak A Kaji, Susmita Sahoo, Joshua M Hare, Roger J Hajjar, Eric A Sobie, Kevin D Costa
Rationale: Myocardial delivery of human mesenchymal stem cells (hMSCs) is an emerging therapy for treating the failing heart. However, the relative effects of hMSC-mediated heterocellular coupling (HC) and paracrine signaling (PS) on human cardiac contractility and arrhythmogenicity remain unresolved. Objective: To better understand hMSC PS and HC effects on human cardiac contractility and arrhythmogenicity by integrating experimental and computational approaches. Methods and Results: : Extending our previous hMSC-cardiomyocyte HC computational model, we incorporated experimentally calibrated hMSC PS effects on cardiomyocyte L-type calcium channel/SERCA activity and cardiac tissue fibrosis...
June 22, 2017: Circulation Research
https://www.readbyqxmd.com/read/28642036/transcription-factor-decoy-technology-a-therapeutic-update
#18
REVIEW
Markus Hecker, Andreas H Wagner
Targeting transcription factors represents one possibility to interfere with a known activated regulatory pathway that promotes disease. Double-stranded transcription factor decoy (TFD) oligodeoxynucleotides (ODN) are therapeutic drug candidates, which are able to specifically target and neutralize key transcription factors involved in the pathogenesis of a given disease. These short double-stranded TFD molecules mimic the consensus DNA binding site of a specific transcription factor in the promoter region of its target genes...
June 19, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28641543/zein-based-nanocarriers-as-potential-natural-alternatives-for-drug-and-gene-delivery-focus-on-cancer-therapy
#19
Ahmed Elzoghby, May Freag, Hadeer Mamdouh, Kadria Elkhodairy
Protein nanocarriers possess unique merits including minimal cytotoxicity, numerous renewable sources, and high drug-binding capability. In opposition to delivery carriers utilizing hydrophilic animal proteins, hydrophobic plant proteins (e.g, zein) have great tendency in fabricating controlled-release particulate carriers without additional chemical modification to stiffen them, which in turn evades the use of toxic chemical crosslinkers. Moreover, zein is related to a class of alcohol-soluble prolamins and generally recognized as safe (GRAS) carrier for drug delivery...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28641542/functional-nanoparticles-and-their-interactions-with-mesenchymal-stem-cells
#20
Weiwei Wang, Zijun Deng, Xun Xu, Zhengdong Li, Friedrich Jung, Nan Ma, Andreas Lendlein
Mesenchymal stem cells (MSCs) have become one of the most important cell sources for regenerative medicine. However, some mechanisms of MSC-based therapy are still not fully understood. The clinical outcome may be restricted by some MSC-related obstacles such as the low survival rate, differentiation into undesired lineages and malignant transformation. In recent years, with the emergence of nanotechnology, various types of multifunctional nanoparticles (NPs) have been designed, prepared and explored for bio-related applications...
June 22, 2017: Current Pharmaceutical Design
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