MAR-Mediated Integration of Plasmid Vectors for In Vivo Gene Transfer and Regulation
News Dec 05, 2013
In this study, scientists devised vectors allowing a tight regulation of transgene expression in mice from such non-viral vectors using a doxycycline-controlled network of activator and repressor proteins. Using these vectors, we demonstrate proper physiological response as consequence of the induced expression of two therapeutically relevant proteins, namely erythropoietin and utrophin. Kinetic studies showed that the induction of transgene expression was only transient, unless epigenetic regulatory elements termed Matrix Attachment Regions, or MAR, were inserted upstream of the regulated promoters. Using episomal plasmid rescue and quantitative PCR assays, we observed that similar amounts of plasmids remained in muscles after electrotransfer with or without MAR elements, but that a significant portion had integrated into the muscle fiber chromosomes. Interestingly, the MAR elements were found to promote plasmid genomic integration but to oppose silencing effects in vivo, thereby mediating long-term expression.
This article is published online in BMC Molecular Biology and is free to access.
Scientists at McGill have found the answer to a question that perplexed Charles Darwin; if natural selection works at the level of the individual, fighting for survival and reproduction, how can a single colony produce worker ants that are so dramatically different in size – from “minor” workers to large-headed soldiers with huge mandibles – especially if they are sterile?
Scientists have developed a successful method to make truly personalized predictions of future disease outcomes for patients with certain types of chronic blood cancers. The study combined extensive genetic and clinical information to predict the prognosis for patients with myeloproliferative neoplasms.
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