journal
MENU ▼
Read by QxMD icon Read
search

Molecular Therapy: the Journal of the American Society of Gene Therapy

journal
https://read.qxmd.com/read/30773447/two-decades-of-molecular-therapy-and-a-35-year-personal-view-of-changes-in-gene-therapy
#1
EDITORIAL
David A Williams
No abstract text is available yet for this article.
February 14, 2019: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://read.qxmd.com/read/30765324/micro-dystrophin-genes-bring-hope-of-an-effective-therapy-for-duchenne-muscular-dystrophy
#2
Kay E Davies, Simon Guiraud
No abstract text is available yet for this article.
February 12, 2019: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://read.qxmd.com/read/30765323/cartilage-targeted-igf-1-treatment-to-promote-longitudinal-bone-growth
#3
Julian C Lui, Max Colbert, Crystal Sao Fong Cheung, Michal Ad, Audrey Lee, Zhongyu Zhu, Kevin M Barnes, Dimiter S Dimitrov, Jeffrey Baron
Recombinant human growth hormone (GH) is commonly used to treat short stature in children. However, GH treatment has limited efficacy, particularly in severe, non-GH-deficient conditions such as chondrodysplasias, and potential off-target effects. Because short stature results from decreased growth plate chondrogenesis, we developed a cartilage-targeting single-chain human antibody fragment (CaAb) aiming to deliver therapeutic molecules to the growth plate, thereby increasing treatment efficacy while minimizing adverse effects on other tissues...
February 1, 2019: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://read.qxmd.com/read/30772143/protease-activatable-adeno-associated-virus-vector-for-gene-delivery-to-damaged-heart-tissue
#4
Caitlin M Guenther, Mitchell J Brun, Antonette D Bennett, Michelle L Ho, Weitong Chen, Banghe Zhu, Michael Lam, Momona Yamagami, Sunkuk Kwon, Nilakshee Bhattacharya, Duncan Sousa, Annicka C Evans, Julie Voss, Eva M Sevick-Muraca, Mavis Agbandje-McKenna, Junghae Suh
Adeno-associated virus (AAV) has emerged as a promising gene delivery vector because of its non-pathogenicity, simple structure and genome, and low immunogenicity compared to other viruses. However, its adoption as a safe and effective delivery vector for certain diseases relies on altering its tropism to deliver transgenes to desired cell populations. To this end, we have developed a protease-activatable AAV vector, named provector, that responds to elevated extracellular protease activity commonly found in diseased tissue microenvironments...
January 29, 2019: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://read.qxmd.com/read/30718090/development-of-novel-micro-dystrophins-with-enhanced-functionality
#5
Julian N Ramos, Katrin Hollinger, Niclas E Bengtsson, James M Allen, Stephen D Hauschka, Jeffrey S Chamberlain
Gene therapies using adeno-associated viral (AAV) vectors have advanced into clinical trials for several diseases, including Duchenne muscular dystrophy (DMD). A limitation of AAV is the carrying capacity (∼5 kb) available for genes and regulatory cassettes (RCs). These size constraints are problematic for the 2.2-Mb dystrophin gene. We previously designed a variety of miniaturized micro-dystrophins (μDys) that displayed significant, albeit incomplete, function in striated muscles. To develop μDys proteins with improved performance, we explored structural modifications of the dystrophin central rod domain...
January 25, 2019: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://read.qxmd.com/read/30765325/mir-221-222-mediated-inhibition-of-autophagy-promotes-dexamethasone-resistance-in-multiple-myeloma
#6
Jian Xu, Yan Su, Aoshuang Xu, Fengjuan Fan, Shidai Mu, Lei Chen, Zhangbo Chu, Bo Zhang, Haifan Huang, Jiasi Zhang, Jun Deng, Lisha Ai, Chunyan Sun, Yu Hu
Inherent or acquired resistance to chemotherapeutic drugs is still an obstacle for the treatment of multiple myeloma (MM). MicroRNA dysregulation is related to the development of chemoresistance in cancers. However, its role in chemoresistance of MM is largely unknown. Here we demonstrated that miR-221/222 were upregulated in plasma cells from patients with MM, especially those with relapsed or refractory disease. Moreover, expression levels of miR-221/222 were inversely correlated with dexamethasone (Dex) sensitivity of human MM cell lines...
January 24, 2019: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://read.qxmd.com/read/30765322/systemic-blockade-of-acvr2b-ligands-protects-myocardium-from-acute-ischemia-reperfusion-injury
#7
Johanna Magga, Laura Vainio, Teemu Kilpiö, Juha J Hulmi, Saija Taponen, Ruizhu Lin, Markus Räsänen, Zoltán Szabó, Erhe Gao, Lea Rahtu-Korpela, Tarja Alakoski, Johanna Ulvila, Mika Laitinen, Arja Pasternack, Walter J Koch, Kari Alitalo, Riikka Kivelä, Olli Ritvos, Risto Kerkelä
Activin A and myostatin, members of the transforming growth factor (TGF)-β superfamily of secreted factors, are potent negative regulators of muscle growth, but their contribution to myocardial ischemia-reperfusion (IR) injury is not known. The aim of this study was to investigate if activin 2B (ACVR2B) receptor ligands contribute to myocardial IR injury. Mice were treated with soluble ACVR2B decoy receptor (ACVR2B-Fc) and subjected to myocardial ischemia followed by reperfusion for 6 or 24 h. Systemic blockade of ACVR2B ligands by ACVR2B-Fc was protective against cardiac IR injury, as evidenced by reduced infarcted area, apoptosis, and autophagy and better preserved LV systolic function following IR...
January 24, 2019: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://read.qxmd.com/read/30713086/endogenously-expressed-antigens-bind-mammalian-rna-via-cationic-domains-that-enhance-priming-of-effector-cd8-t-cells-by-dna-vaccination
#8
Jana Krieger, Petra Riedl, Katja Stifter, Gleyder Roman-Sosa, Thomas Seufferlein, Martin Wagner, Reinhold Schirmbeck
Hepatitis B virus (HBV) core (HBV-C) antigens with homologous or heterologous HIV-tat48-57-like (HBV-C149tat) cationic domains non-specifically bind cellular RNA in vector-transfected cells. Here, we investigated whether RNA-binding to cationic domains influences the immunogenicity of endogenously expressed antigens delivered by DNA vaccination. We initially evaluated induction of HBV-C (Kb /C93)-specific CD8+ T cell responses in C57BL/6J (B6) and 1.4HBV-Smut transgenic (tg) mice that harbor a replicating HBV genome in hepatocytes by DNA immunization...
January 22, 2019: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://read.qxmd.com/read/30711446/exosome-mediated-mir-29-transfer-reduces-muscle-atrophy-and-kidney-fibrosis-in-mice
#9
Haidong Wang, Bin Wang, Aiqing Zhang, Faten Hassounah, Yiqi Seow, Matthew Wood, Fuying Ma, Janet D Klein, S Russ Price, Xiaonan H Wang
Our previous study showed that miR-29 attenuates muscle wasting in chronic kidney disease. Other studies found that miR-29 has anti-fibrosis activity. We hypothesized that intramuscular injection of exosome-encapsulated miR-29 would counteract unilateral ureteral obstruction (UUO)-induced muscle wasting and renal fibrosis. We used an engineered exosome vector, which contains an exosomal membrane protein gene Lamp2b that was fused with the targeting peptide RVG (rabies viral glycoprotein peptide). RVG directs exosomes to organs that express the acetylcholine receptor, such as kidney...
January 18, 2019: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://read.qxmd.com/read/30665748/the-future-of-the-molecular-therapy-journal-family-change-is-inevitable-growth-is-optional
#10
EDITORIAL
Robert M Frederickson
No abstract text is available yet for this article.
January 18, 2019: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://read.qxmd.com/read/30711447/raavrh74-mck-galgt2-protects-against-loss-of-hemodynamic-function-in-the-aging-mdx-mouse-heart
#11
Rui Xu, Ying Jia, Deborah A Zygmunt, Paul T Martin
Dilated cardiomyopathy is a common cause of death in patients with Duchenne muscular dystrophy (DMD). Gene therapies for DMD must, therefore, have a therapeutic impact in cardiac as well as skeletal muscles. Our previous studies have shown that GALGT2 overexpression in mdx skeletal muscles can prevent muscle damage. Here we have tested whether rAAVrh74.MCK.GALGT2 gene therapy in mdx cardiac muscle can prevent the loss of heart function. Treatment of mdx hearts with rAAVrh74.MCK.GALGT2 1 day after birth did not negatively alter hemodynamic function, tested at 3 months of age, and it prevented early left ventricular remodeling and expression of fibrotic gene markers...
January 15, 2019: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://read.qxmd.com/read/30692016/circrna-33186-contributes-to-the-pathogenesis-of-osteoarthritis-by-sponging-mir-127-5p
#12
Zhi-Bin Zhou, Gao-Xiang Huang, Qiang Fu, Bin Han, Jia-Jia Lu, Ai-Min Chen, Lei Zhu
Osteoarthritis (OA), the most prevalent age-related joint disorder, is characterized by chronic inflammation, progressive articular cartilage destruction, and subchondral bone sclerosis. Accumulating evidences indicate that circular RNAs (circRNAs) play a critical role in various diseases, but the function of circRNAs in OA remains largely unknown. Here we showed that circRNA.33186 was significantly upregulated in IL-1β)-treated chondrocytes and in cartilage tissues of a destabilized medial meniscus (DMM)-induced OA mouse model...
January 15, 2019: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://read.qxmd.com/read/30713087/oral-gavage-of-ginger-nanoparticle-derived-lipid-vectors-carrying-dmt1-sirna-blunts-iron-loading-in-murine-hereditary-hemochromatosis
#13
Xiaoyu Wang, Mingzhen Zhang, Shireen R L Flores, Regina R Woloshun, Chunhua Yang, Liangjie Yin, Ping Xiang, Xiaodong Xu, Michael D Garrick, Sadasivan Vidyasagar, Didier Merlin, James F Collins
Nanoparticles (NPs) have been utilized to deliver drugs to the intestinal epithelium in vivo. Moreover, NPs derived from edible plants are less toxic than synthetic NPs. Here, we utilized ginger NP-derived lipid vectors (GDLVs) in a proof-of-concept investigation to test the hypothesis that inhibiting expression of divalent metal-ion transporter 1 (Dmt1) would attenuate iron loading in a mouse model of hereditary hemochromatosis (HH). Initial experiments using duodenal epithelial organ cultures from intestine-specific Dmt1 knockout (KO) (Dmt1int/int ) mice in the Ussing chamber established that Dmt1 is the only active iron importer during iron-deficiency anemia...
January 12, 2019: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://read.qxmd.com/read/30704961/anti-drug-antibody-responses-impair-prophylaxis-mediated-by-aav-delivered-hiv-1-broadly-neutralizing-antibodies
#14
Matthew R Gardner, Ina Fetzer, Lisa M Kattenhorn, Meredith E Davis-Gardner, Amber S Zhou, Barnett Alfant, Jesse A Weber, Hema R Kondur, Jose M Martinez-Navio, Sebastian P Fuchs, Ronald C Desrosiers, Guangping Gao, Jeffrey D Lifson, Michael Farzan
Adeno-associated virus (AAV) delivery of potent and broadly neutralizing antibodies (bNAbs is a promising approach for the prevention of HIV-1 infection. The immunoglobulin G (IgG)1 subtype is usually selected for this application, because it efficiently mediates antibody effector functions and has a somewhat longer half-life. However, the use of IgG1-Fc has been associated with the generation of anti-drug antibodies (ADAs) that correlate with loss of antibody expression. In contrast, we have shown that expression of the antibody-like molecule eCD4-Ig bearing a rhesus IgG2-Fc domain showed reduced immunogenicity and completely protected rhesus macaques from simian-HIV (SHIV)-AD8 challenges...
January 12, 2019: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://read.qxmd.com/read/30660488/dancr-promotes-metastasis-and-proliferation-in-bladder-cancer-cells-by-enhancing-il-11-stat3-signaling-and-ccnd1-expression
#15
Ziyue Chen, Xu Chen, Ruihui Xie, Ming Huang, Wen Dong, Jinli Han, Jingtong Zhang, Qianghua Zhou, Hui Li, Jian Huang, Tianxin Lin
The prognosis for patients with bladder cancer (BCa) with lymph node (LN) metastasis is poor, and it is not improved by current treatments. Long noncoding RNAs (lncRNAs) are involved in the pathology of various tumors, including BCa. However, the role of Differentiation antagonizing non-protein coding RNA (DANCR) in BCa LN metastasis remains unclear. In this study, we discover that DANCR was significantly upregulated in BCa tissues and cases with LN metastasis. DANCR expression was positively correlated with LN metastasis status, tumor stage, histological grade, and poor patient prognosis...
January 9, 2019: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://read.qxmd.com/read/30770173/self-amplifying-rna-vaccines-for-venezuelan-equine-encephalitis-virus-induce-robust-protective-immunogenicity-in-mice
#16
Marcelo M Samsa, Lesley C Dupuy, Clayton W Beard, Carolyn M Six, Connie S Schmaljohn, Peter W Mason, Andrew J Geall, Jeffrey B Ulmer, Dong Yu
Venezuelan equine encephalitis virus (VEEV) is a known biological defense threat. A live-attenuated investigational vaccine, TC-83, is available, but it has a high non-response rate and can also cause severe reactogenicity. We generated two novel VEE vaccine candidates using self-amplifying mRNA (SAM). LAV-CNE is a live-attenuated VEE SAM vaccine formulated with synthetic cationic nanoemulsion (CNE) and carrying the RNA genome of TC-83. IAV-CNE is an irreversibly-attenuated VEE SAM vaccine formulated with CNE, delivering a TC-83 genome lacking the capsid gene...
January 7, 2019: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://read.qxmd.com/read/30692017/analyzing-the-interactions-of-mrnas-and-ncrnas-to-predict-competing-endogenous-rna-networks-in-osteosarcoma-chemo-resistance
#17
Kun-Peng Zhu, Chun-Lin Zhang, Xiao-Long Ma, Jian-Ping Hu, Tao Cai, Lei Zhang
Chemo-resistance is a huge obstacle encountered in the osteosarcoma (OS) treatment. Protein-coding mRNAs, as well as non-coding RNAs (ncRNAs), including long ncRNA (lncRNA), circular RNA (circRNA), and microRNA (miRNA), have been demonstrated to play an essential role in the regulation of cancer biology. However, the comprehensive expression profile and competing endogenous RNA (ceRNA) regulatory network between mRNAs and ncRNAs in the OS chemo-resistance still remain unclear. In the current study, we developed whole-transcriptome sequencing (RNA sequencing [RNA-seq]) in the three paired multi-drug chemo-resistant and chemo-sensitive OS cell lines to comprehensively identify differentially expressed lncRNAs, circRNAs, miRNAs, and mRNAs...
January 7, 2019: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://read.qxmd.com/read/30686588/targeted-allele-suppression-prevents-progressive-hearing-loss-in-the-mature-murine-model-of-human-tmc1-deafness
#18
Hidekane Yoshimura, Seiji B Shibata, Paul T Ranum, Hideaki Moteki, Richard J H Smith
Hearing loss is the most common human sensory deficit. Its correction has been the goal of several gene-therapy based studies exploring a variety of interventions. Although these studies report varying degrees of success, all treatments have targeted developing inner ears in neonatal mice, a time point in the structural maturation of the cochlea prior to 26 weeks gestational age in humans. It is unclear whether cochlear gene therapy can salvage hearing in the mature organ of Corti. Herein, we report the first study to test gene therapy in an adult murine model of human deafness...
January 7, 2019: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://read.qxmd.com/read/30655211/delivery-of-mrna-therapeutics-for-the-treatment-of-hepatic-diseases
#19
REVIEW
Zeljka Trepotec, Eva Lichtenegger, Christian Plank, Manish K Aneja, Carsten Rudolph
Promising improvements in the field of transcript therapeutics have clearly enhanced the potential of mRNA as a new pillar for protein replacement therapies. Synthetic mRNAs are engineered to replace mutated mRNAs and to be immunologically inconspicuous and highly stable while maximizing protein expression. Approaches to deliver mRNA into the cellular cytoplasm safely and efficiently have been further developed so that two mRNA-based approaches replacing vascular endothelial growth factor (VEGF) and cystic fibrosis transmembrane conductance regulator (CFTR) have now made it into clinical trials...
December 22, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://read.qxmd.com/read/30638957/improving-mrna-based-therapeutic-gene-delivery-by-expression-augmenting-3-utrs-identified-by-cellular-library-screening
#20
Alexandra G Orlandini von Niessen, Marco A Poleganov, Corina Rechner, Arianne Plaschke, Lena M Kranz, Stephanie Fesser, Mustafa Diken, Martin Löwer, Britta Vallazza, Tim Beissert, Valesca Bukur, Andreas N Kuhn, Özlem Türeci, Ugur Sahin
Synthetic mRNA has emerged as a powerful tool for the transfer of genetic information, and it is being explored for a variety of therapeutic applications. Many of these applications require prolonged intracellular persistence of mRNA to improve bioavailability of the encoded protein. mRNA molecules are intrinsically unstable and their intracellular kinetics depend on the UTRs embracing the coding sequence, in particular the 3' UTR elements. We describe here a novel and generally applicable cell-based selection process for the identification of 3' UTRs that augment the expression of proteins encoded by synthetic mRNA...
December 18, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
journal
journal
34730
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"