Hydrodynamic tail vein (HTV) delivery is a simple and rapid tail vein injection method of a high volume of naked plasmid DNA resulting in high levels of foreign gene expression in organs, especially the liver. Compared to other organs, HTV delivery results in more than a 1000-fold higher transgene expression in liver. After being bitten by malaria-infected mosquitoes, malaria parasites transiently infect the host liver and form the liver stages. The liver stages are known to be the key target for CD8+ T cells that mediate protective anti-malaria immunity in an animal model. Therefore, in this study, we utilized the HTV delivery technique as a tool to determine the in vivo cytotoxic effect of malaria antigen-specific CD8+ T cells. Two weeks after mice were immunized with recombinant adenoviruses expressing malarial antigens, the immunized mice as well as naïve mice were challenged by HTV delivery of naked plasmid DNA co-encoding respective antigen together with luciferase using dual promoters. Three days after the HTV challenge, non-invasive whole-body bioluminescent imaging was performed. The images demonstrate in vivo activity of CD8+ T cells against malaria antigen-expressing cells in liver.
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http://dx.doi.org/10.3390/biom2010023 | DOI Listing |
Mol Ther Methods Clin Dev
December 2022
Division of Metabolism and Children's Research Center, University Children's Hospital Zürich, Steinwiesstrasse 75, 8032 Zürich, Switzerland.
Hydrodynamic tail vein injection (HTV) is the "gold standard" for delivering naked DNA vectors to mouse liver, thereby transfecting predominately perivenous hepatocytes. While HTV corrects metabolic liver defects such as phenylketonuria or cystathionine β-synthase deficiency, correction of mice with ornithine transcarbamylase (OTC) deficiency was not possible despite overexpression in the liver, as the OTC enzyme is primarily expressed in periportal hepatocytes. To target periportal hepatocytes, we established hydrodynamic retrograde intrabiliary injection (HRII) in mice and optimized minicircle (MC) vector delivery using luciferase as a marker gene.
View Article and Find Full Text PDFInt J Environ Res Public Health
February 2021
Centre for Social Impact, Faculty of Business and Law, Swinburne University of Technology, P.O. Box 218, Mail H25, Hawthorn, VIC 3122, Australia.
Unlabelled: Prevention systems improve the performance of health promotion interventions. This research describes the establishment of the Australian state government initiative, Healthy Together Victoria's (HTV) macro infrastructure for the delivery of large-scale prevention interventions.
Methods: This paper reports on findings of 31 semi-structured interviews about participants' understanding of systems thinking and their reflections of the strengths and weaknesses of the HTV prevention system.
J Toxicol Environ Health B Crit Rev
August 2019
a Health Effects Laboratory Division , National Institute for Occupational Safety and Health, Morgantown , WV , USA.
Workers in a number of different occupational sectors are exposed to workplace vibration on a daily basis. This exposure may arise through the use of powered-hand tools or hand-transmitted vibration (HTV). Workers might also be exposed to whole body vibration (WBV) by driving delivery vehicles, earth moving equipment, or through use of tools that generate vibration at low dominant frequencies and high amplitudes, such as jackhammers.
View Article and Find Full Text PDFJ Pharmacol Exp Ther
February 2019
Cardiovascular, Renal and Metabolism Translational Medicine Unit, Early Clinical Development, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden (C.K., P.J.G.); Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden (C.K.); Emeriti Pharma, AZ Bioventure Hub, Gothenburg, Sweden (D.G.); and KW Translational Medicine AB, Västra Frölunda, Sweden (K.W.).
Fewer new medicines have become available to patients during the last decades. Clinical efficacy failures in late-phase development have been identified as a common cause of this decline. Improved ways to ensure early selection of the right drug targets when it comes to efficacy is therefore a highly desirable goal.
View Article and Find Full Text PDFBiol Pharm Bull
May 2016
Faculty of Pharmaceutical Sciences, Hokkaido University.
Plasmid DNA (pDNA) is expected to be a new class of medicine for treating currently incurable diseases. To deliver these nucleic acids, we developed a liposomal delivery system we have called a multifunctional envelope-type nano device (MEND). In this report, we demonstrate that a MEND containing a pH-sensitive cationic lipid, YSK05 (YSK-MEND), efficiently delivered pDNA via systemic injection, and that its expression was highly dependent on the encapsulation state of the pDNA.
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