journal
MENU ▼
Read by QxMD icon Read
search

Molecular Therapy. Methods & Clinical Development

journal
https://www.readbyqxmd.com/read/29159202/a-humoral-immune-response-alters-the-distribution-of-enzyme-replacement-therapy-in-murine-mucopolysaccharidosis-type-i
#1
Steven Q Le, Shih-Hsin Kan, Don Clarke, Valentina Sanghez, Martin Egeland, Kristen N Vondrak, Terence M Doherty, Moin U Vera, Michelina Iacovino, Jonathan D Cooper, Mark S Sands, Patricia I Dickson
Antibodies against recombinant proteins can significantly reduce their effectiveness in unanticipated ways. We evaluated the humoral response of mice with the lysosomal storage disease mucopolysaccharidosis type I treated with weekly intravenous recombinant human alpha-l-iduronidase (rhIDU). Unlike patients, the majority of whom develop antibodies to recombinant human alpha-l-iduronidase, only approximately half of the treated mice developed antibodies against recombinant human alpha-l-iduronidase and levels were low...
March 16, 2018: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29159201/interactions-between-retroviruses-and-the-host-cell-genome
#2
REVIEW
Valentina Poletti, Fulvio Mavilio
Replication-defective retroviral vectors have been used for more than 25 years as a tool for efficient and stable insertion of therapeutic transgenes in human cells. Patients suffering from severe genetic diseases have been successfully treated by transplantation of autologous hematopoietic stem-progenitor cells (HSPCs) transduced with retroviral vectors, and the first of this class of therapies, Strimvelis, has recently received market authorization in Europe. Some clinical trials, however, resulted in severe adverse events caused by vector-induced proto-oncogene activation, which showed that retroviral vectors may retain a genotoxic potential associated to proviral integration in the human genome...
March 16, 2018: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29159200/analyzing-the-genotoxicity-of-retroviral-vectors-in-hematopoietic-cell-gene-therapy
#3
REVIEW
Luca Biasco, Michael Rothe, Hildegard Büning, Axel Schambach
Retroviral vectors, including those derived from gammaretroviruses and lentiviruses, have found their way into the clinical arena and demonstrated remarkable efficacy for the treatment of immunodeficiencies, leukodystrophies, and globinopathies. Despite these successes, gene therapy unfortunately also has had to face severe adverse events in the form of leukemias and myelodysplastic syndromes, related to the semi-random vector integration into the host cell genome that caused deregulation of neighboring proto-oncogenes...
March 16, 2018: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29034262/detection-of-replication-competent-lentivirus-using-a-qpcr-assay-for-vsv-g
#4
Lindsey M Skrdlant, Randall J Armstrong, Brett M Keidaisch, Mario F Lorente, David L DiGiusto
Lentiviral vectors are a common tool used to introduce new and corrected genes into cell therapy products for treatment of human diseases. Although lentiviral vectors are ideal for delivery and stable integration of genes of interest into the host cell genome, they potentially pose risks to human health, such as integration-mediated transformation and generation of a replication competent lentivirus (RCL) capable of infecting non-target cells. In consideration of the latter risk, all cell-based products modified by lentiviral vectors and intended for patient use must be tested for RCL prior to treatment of the patient...
March 16, 2018: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29159199/dna-mediated-gene-therapy-in-a-mouse-model-of-limb-girdle-muscular-dystrophy-2b
#5
Julia Ma, Christophe Pichavant, Haley du Bois, Mital Bhakta, Michele P Calos
Mutations in the gene for dysferlin cause a degenerative disorder of skeletal muscle known as limb girdle muscular dystrophy 2B. To achieve gene delivery of plasmids encoding dysferlin to hind limb muscles of dysferlin knockout mice, we used a vascular injection method that perfused naked plasmid DNA into all major muscle groups of the hind limb. We monitored delivery by luciferase live imaging and western blot, confirming strong dysferlin expression that persisted over the 3-month time course of the experiment...
December 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29085848/rapid-generation-of-multiple-loci-engineered-marker-free-poxvirus-and-characterization-of-a-clinical-grade-oncolytic-vaccinia-virus
#6
Zong Sheng Guo, Zuqiang Liu, Magesh Sathaiah, Jiahu Wang, Roshni Ravindranathan, Eun Kim, Shaohua Huang, Thomas W Kenniston, John C Bell, Herbert J Zeh, Lisa H Butterfield, Andrea Gambotto, David L Bartlett
Recombinant poxviruses, utilized as vaccine vectors and oncolytic viruses, often require manipulation at multiple genetic loci in the viral genome. It is essential for viral vectors to possess no adventitious mutations and no (antibiotic) selection marker in the final product for human patients in order to comply with the guidance from the regulatory agencies. Rintoul et al. have previously developed a selectable and excisable marker (SEM) system for the rapid generation of recombinant vaccinia virus. In the current study, we describe an improved methodology for rapid creation and selection of recombinant poxviruses with multiple genetic manipulations solely based on expression of a fluorescent protein and with no requirement for drug selection that can lead to cellular stress and the risk of adventitious mutations throughout the viral genome...
December 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29057281/atg5-flox-derived-autophagy-deficient-model-of-pompe-disease-does-it-tell-the-whole-story
#7
REVIEW
Jeong-A Lim, Hossein Zare, Rosa Puertollano, Nina Raben
No abstract text is available yet for this article.
December 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29034261/in%C3%A2-vivo-production-of-monoclonal-antibodies-by-gene-transfer-via-electroporation-protects-against-lethal-influenza-and-ebola-infections
#8
Chasity D Andrews, Yang Luo, Ming Sun, Jian Yu, Arthur J Goff, Pamela J Glass, Neal N Padte, Yaoxing Huang, David D Ho
Monoclonal antibodies (mAbs) have wide clinical utility, but global access is limited by high costs and impracticalities associated with repeated passive administration. Here, we describe an optimized electroporation-based DNA gene transfer platform technology that can be utilized for production of functional mAbs in vivo, with the potential to reduce costs and administration burdens. We demonstrate that multiple mAbs can be simultaneously expressed at protective concentrations for a protracted period of time using DNA doses and electroporation conditions that are feasible clinically...
December 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29034260/clodronate-improves-survival-of-transplanted-hoxb8-myeloid-progenitors-with-constitutively-active-gmcsfr-in-immunocompetent-mice
#9
Simon Lee, Saul Kivimäe, Francis C Szoka
New methods to produce large numbers of myeloid progenitor cells, precursors to macrophages (MΦs), by maintaining Hoxb8 transcription factor activity(1) has reinvigorated interest in MΦ cell therapies. We generated Hoxb8-dependent myeloid progenitors (HDPs) by transducing lineage-negative bone marrow cells with a constitutively expressed Hoxb8 flanked by loxP. HDPs proliferate indefinitely and differentiate into MΦ when Hoxb8 is removed by a tamoxifen-inducible Cre. We genetically modified HDPs with a constitutively active GMCSF receptor and the tamoxifen-induced transcription factor IRF8, which we have termed "HDP-on...
December 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29018836/one-step-fabrication-of-bone-morphogenetic-protein-2-gene-activated-porous-poly-l-lactide-scaffold-for-bone-induction
#10
Jingwen Xue, Hang Lin, Allison Bean, Ying Tang, Jian Tan, Rocky S Tuan, Bing Wang
Bone morphogenetic protein 2 (BMP2) is an efficacious inducer for the osteogenesis of mesenchymal stem cells (MSCs). Conventional applications of BMP2 have involved either the direct incorporation of BMP2 protein or ex vivo BMP2 gene transfer into stem cells prior to their transplantation. These approaches are able to promote bone formation to some extent; however, they are hampered by either the lack of stability and sustainability of BMP2 protein or the time-consuming and cost-prohibitive in vitro cell culture procedure...
December 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29018835/-13-c-31-p-mrs-metabolic-biomarkers-of-disease-progression-and-response-to-aav-delivery-of-hgaa-in-a-mouse-model-of-pompe-disease
#11
Celine Baligand, Adrian G Todd, Brittany Lee-McMullen, Ravneet S Vohra, Barry J Byrne, Darin J Falk, Glenn A Walter
The development of therapeutic clinical trials for glycogen storage disorders, including Pompe disease, has called for non-invasive and objective biomarkers. Glycogen accumulation can be measured in vivo with (13)C MRS. However, clinical implementation remains challenging due to low signal-to-noise. On the other hand, the buildup of glycolytic intermediates may be detected with (31)P MRS. We sought to identify new biomarkers of disease progression in muscle using (13)C/(31)P MRS and (1)H HR-MAS in a mouse model of Pompe disease (Gaa(-/-))...
December 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29018834/in-situ-liver-expression-of-hbsag-cd3-bispecific-antibodies-for-hbv-immunotherapy
#12
Robert L Kruse, Thomas Shum, Xavier Legras, Mercedes Barzi, Frank P Pankowicz, Stephen Gottschalk, Karl-Dimiter Bissig
Current therapies against hepatitis B virus (HBV) do not reliably cure chronic infection, necessitating new therapeutic approaches. The T cell response can clear HBV during acute infection, and the adoptive transfer of antiviral T cells during bone marrow transplantation can cure patients of chronic HBV infection. To redirect T cells to HBV-infected hepatocytes, we delivered plasmids encoding bispecific antibodies directed against the viral surface antigen (HBsAg) and CD3, expressed on almost all T cells, directly into the liver using hydrodynamic tail vein injection...
December 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28971109/accelerating-patients-access-to-advanced-therapies-in-the-eu
#13
REVIEW
Ahmed Elsanhoury, Ralf Sanzenbacher, Petra Reinke, Mohamed Abou-El-Enein
No abstract text is available yet for this article.
December 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28948187/profiling-the-targets-of-protective-cd8-t-cell-responses-to-infection
#14
Joseph T Bruder, Ping Chen, Greg Ekberg, Emily C Smith, Christopher A Lazarski, Bennett A Myers, Jessica Bolton, Martha Sedegah, Eileen Villasante, Thomas L Richie, C Richter King, Joao C Aguiar, Denise L Doolan, Douglas E Brough
T cells are critical effectors of host immunity that target intracellular pathogens, such as the causative agents of HIV, tuberculosis, and malaria. The development of vaccines that induce effective cell-mediated immunity against such pathogens has proved challenging; for tuberculosis and malaria, many of the antigens targeted by protective T cells are not known. Here, we report a novel approach for screening large numbers of antigens as potential targets of T cells. Malaria provides an excellent model to test this antigen discovery platform because T cells are critical mediators of protection following immunization with live sporozoite vaccines and the specific antigen targets are unknown...
December 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28879213/dna-loaded-cationic-liposomes-efficiently-function-as-a-vaccine-against-malarial-proteins
#15
Wesley L Fotoran, Rachele Santangelo, Beatriz N M de Miranda, Darrell J Irvine, Gerhard Wunderlich
The delivery of antigens as DNA vaccines is an efficient alternative to induce immune responses against antigens, which are difficult to produce in recombinant form. However, the delivery of naked DNA is ineffective or relies on sophisticated ballistic devices. Here, we show a combination of liposome application and naked DNA vaccine that successfully overcomes these problems. Upon entrapment of plasmids encoding different antigens in cationic particles, transfection efficiencies similar to commercial kits were achieved in in vitro cell cultures...
December 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28932757/a-five-repeat-micro-dystrophin-gene-ameliorated-dystrophic-phenotype-in-the-severe-dba-2j-mdx-model-of-duchenne-muscular-dystrophy
#16
Chady H Hakim, Nalinda B Wasala, Xiufang Pan, Kasun Kodippili, Yongping Yue, Keqing Zhang, Gang Yao, Brittney Haffner, Sean X Duan, Julian Ramos, Joel S Schneider, N Nora Yang, Jeffrey S Chamberlain, Dongsheng Duan
Micro-dystrophins are highly promising candidates for treating Duchenne muscular dystrophy, a lethal muscle disease caused by dystrophin deficiency. Here, we report robust disease rescue in the severe DBA/2J-mdx model with a neuronal nitric oxide synthase (nNOS)-binding micro-dystrophin vector. 2 × 10(13) vector genome particles/mouse of the vector were delivered intravenously to 10-week-old mice and were evaluated at 6 months of age. Saturated micro-dystrophin expression was detected in all skeletal muscles and the heart and restored the dystrophin-associated glycoprotein complex and nNOS...
September 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28932756/non-clinical-safety-and-efficacy-of-an-aav2-8-vector-administered-intravenously-for-treatment-of-mucopolysaccharidosis-type-vi
#17
Rita Ferla, Marialuisa Alliegro, Jean-Brice Marteau, Margherita Dell'Anno, Edoardo Nusco, Severine Pouillot, Stefania Galimberti, Maria Grazia Valsecchi, Vincent Zuliani, Alberto Auricchio
In vivo gene therapy with adeno-associated viral (AAV) vectors is safe and effective in humans. We recently demonstrated that AAV8-mediated liver gene transfer is effective in animal models of mucopolysaccharidosis type VI (MPS VI), a rare lysosomal storage disease that is caused by arylsulfatase B (ARSB) deficiency. In preparing for a first-in-human trial, we performed non-clinical studies to assess the safety of intravenous administrations of AAV2/8.TBG.hARSB produced under good manufacturing practice-like conditions...
September 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28879212/safety-and-efficacy-of-the-complement-inhibitor-amy-101-in-a-natural-model-of-periodontitis-in-non-human-primates
#18
Tetsuhiro Kajikawa, Ruel A Briones, Ranillo R G Resuello, Joel V Tuplano, Edimara S Reis, Evlambia Hajishengallis, Cristina A G Garcia, Despina Yancopoulou, John D Lambris, George Hajishengallis
Periodontitis is a chronic inflammatory disease associated with overactivation of the complement system. Recent preclinical studies suggest that host-modulation therapies may contribute to effective treatment of human periodontitis, which may lead to loss of teeth and function if untreated. We previously showed that locally administered AMY-101 (Cp40), a peptidic inhibitor of the central complement component C3, can inhibit naturally occurring periodontitis in non-human primates (NHPs) when given once a week...
September 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28831401/global-screening-of-antiviral-genes-that-suppress-baculovirus-transgene-expression-in-mammalian-cells
#19
Chia-Hung Wang, Nenavath Gopal Naik, Lin-Li Liao, Sung-Chan Wei, Yu-Chan Chao
Although baculovirus has been used as a safe and convenient gene delivery vector in mammalian cells, baculovirus-mediated transgene expression is less effective in various mammalian cell lines. Identification of the negative regulators in host cells is necessary to improve baculovirus-based expression systems. Here, we performed high-throughput shRNA library screening, targeting 176 antiviral innate immune genes, and identified 43 host restriction factor genes in a human A549 lung carcinoma cell line. Among them, suppression of receptor interaction protein kinase 1 (RIP1, also known as RIPK1) significantly increased baculoviral transgene expression without resulting in significant cell death...
September 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28828393/neonatal-gene-therapy-for-hemophilia-b-by-a-novel-adenovirus-vector-showing-reduced-leaky-expression-of-viral-genes
#20
Shunsuke Iizuka, Fuminori Sakurai, Masashi Tachibana, Kazuo Ohashi, Hiroyuki Mizuguchi
Gene therapy during neonatal and infant stages is a promising approach for hemophilia B, a congenital disorder caused by deficiency of blood coagulation factor IX (FIX). An adenovirus (Ad) vector has high potential for use in neonatal or infant gene therapy for hemophilia B due to its superior transduction properties; however, leaky expression of Ad genes often reduces the transduction efficiencies by Ad protein-mediated tissue damage. Here, we used a novel Ad vector, Ad-E4-122aT, which exhibits a reduction in the leaky expression of Ad genes in liver, in gene therapy studies for neonatal hemophilia B mice...
September 15, 2017: Molecular Therapy. Methods & Clinical Development
journal
journal
48774
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"