In JoVE (1)
Articles by Matthew Dent in JoVE
Efficient Agroinfiltration of Plants for High-level Transient Expression of Recombinant Proteins Kahlin Leuzinger*1, Matthew Dent*1, Jonathan Hurtado1, Jake Stahnke1, Huafang Lai1, Xiaohong Zhou1, Qiang Chen1 1The College of Technology and Innovation, Center for Infectious Disease and Vaccinology, The Biodesign Institute, Arizona State University Plants offer a novel system for the production of pharmaceutical proteins on a commercial scale that is more scalable, cost-efficient and safe than current expression paradigms. In this study, we report a simple and convenient, yet scalable approach to introduce target-gene containing Agrobacterium tumefaciens into plants for protein transient expression.
Other articles by Matthew Dent on PubMed
Application of Toxicokinetics to Improve Chemical Risk Assessment: Implications for the Use of Animals Regulatory Toxicology and Pharmacology : RTP. Dec, 2009 | Pubmed ID: 19665509 While toxicokinetics has become an integral part of pharmaceutical safety assessment over the last two decades, its use in the chemical industry is relatively new. However, it is recognised as a potentially important tool in human health risk assessment and recent initiatives have advocated greater application of toxicokinetics as part of an improved assessment strategy for crop protection chemicals that could offer greater efficiency, use fewer animals and provide better data for risk assessment purposes. To explore the potential scientific and animal welfare benefits of increased use of toxicokinetic data across the chemical industry, an international workshop was held in 2008. Experts from a wide range of chemical industry sectors, including industrial chemicals, agrochemicals and consumer products, participated in the meeting as well as representatives from relevant regulatory authorities. Pharmaceutical industry experts were also invited, in order to share experiences from the extensive use of toxicokinetics in drug development. Given that increased generation of toxicokinetic data could potentially result in an increased number of animals undergoing testing, technologies and strategies to reduce and refine animal use for this purpose were also considered. This paper outlines and expands upon the key themes that emerged from the workshop.
Use of Toxicokinetics to Support Chemical Evaluation: Informing High Dose Selection and Study Interpretation Regulatory Toxicology and Pharmacology : RTP. Mar, 2012 | Pubmed ID: 22198561 Toxicokinetic (TK) information can substantially enhance the value of the data generated from toxicity testing, and is an integral part of pharmaceutical safety assessment. It is less widely used in the chemical, agrochemical and consumer products industries, but recognition of its value is growing, as reflected by increased reference to the use of TK information in new and draft OECD test guidelines. To help promote increased consideration of the important role TK can play in chemical risk assessment, we have gathered practical examples from the peer-reviewed literature, as well as in-house industry data, that highlight opportunities for the use of TK in the selection of dose levels. Use of TK can help to ensure studies are designed to be of most relevance to assessing potential risk in humans, and avoid the use of excessively high doses that could result in unnecessary suffering in experimental animals. Greater emphasis on the potential contribution of TK in guiding study design and interpretation should be incorporated in regulatory data requirements and associated guidance.
Assessing Dose-dependent Differences in DNA-damage, P53 Response and Genotoxicity for Quercetin and Curcumin Toxicology in Vitro : an International Journal Published in Association with BIBRA. Jun, 2013 | Pubmed ID: 23764886 As part of a longer-term goal to create a quantitative mechanistic model of the p53-Mdm2 DNA-damage pathway, we are studying cellular responses to compounds causing DNA-damage by various modes-of action, including two natural polyphenols: quercetin (QUE) and curcumin (CUR). QUE and CUR are weak mutagens in some in vitro assays and possess both anti- or pro-oxidant effects depending on dose. This study examines the dose-response of DNA-damage pathway to these compounds in HT1080 cells (a human cell line with wild-type p53) at doses relevant to human exposure. CUR was more potent in causing reactive oxygen species, DNA damage (measured as phospho-H2AX) and p53 induction, with lowest observed effect levels (LOELs; 3-8Î¼M) approximately three-fold lower than QUE (20-30Î¼M). CUR showed a strong G2/M arrest and apoptosis at âˆ¼10Î¼M. QUE caused S phase arrest at low doses (8Î¼M) and apoptosis was only induced at much higher doses (60Î¼M). At concentrations with similar levels of p-H2AX and p53 biomarkers, CUR caused greater micronuclei frequency. CUR induced clear increases micronuclei at 3-6Î¼M, while QUE had a weaker micronuclei response even at the highest doses. Thus, even with two compounds sharing common chemistries, DNA-damage response patterns differed significantly in terms of dose and cell fate.