In studies to determine how plasmids enter the nuclei of non-dividing cells, the group previously identified a region of a smooth muscle cell-specific promoter that was able to mediate nuclear targeting of any plasmid carrying this sequence uniquely in cultured smooth muscle cells but in no other cell type.
In their current study to appear in the July 08 issue of Experimental Biology and Medicine, the team, led by Drs. David Dean and Jennifer Young from the Department of Medicine at Northwestern University, in collaboration with Warren Zimmer from Texas A & M University, now demonstrate that such restriction of nuclear entry using this specific DNA sequence can be used in blood vessels of living animals to direct gene transfer and expression specifically to smooth muscle cells.
They have also developed a novel gene delivery approach for the vasculature that uses an electric field to transiently permeabilize the plasma membrane of cells to allow entry of DNA. Thus, this work establishes the control of nuclear entry of gene therapy vectors as a novel approach to target genes and gene expression to desired cell types in the body.
Vascular smooth muscle proliferative diseases, including atherosclerosis and restenosis, are among the leading causes of morbidity and mortality in the US. Gene therapy may represent an important alternative for the treatment and prevention of these proliferative diseases of the vasculature. It can be highly cell-specific, mimic or restore normal in vivo function, and can be permanent or transient depending on vector design. Currently, a number of gene delivery systems for use on the arterial wall are being studied, but as yet their low efficiency in gene transfer and lack of cell-specific targeting and expression are major limitations. According to Dr. David Dean, "The benefit of our newly described approach is that it can target specific cell types.
One of the most commonly envisioned treatments for these proliferative disorders is to deliver genes that kill or inhibit the dividing smooth muscle cells, but we need to target only these muscle cells and not any other cell in the vessel wall and this approach will enable us to do just that". The goal of the team is to design more effective gene therapy vectors for use in the vasculature by understanding the molecular mechanisms by which DNA and DNA-protein complexes are actively transported into the nucleus. Dr. Warren Zimmer states "these results set the stage for our future use of this technology to deliver therapeutic genes to lessen the severity of restenosis which is the most common issue following angioplasty and placement of stents".
Dr. Dean continues, "Now that we have demonstrated proof of principle for this approach we can look for DNA sequences that act in other tissues and develop cell-specific treatments for any number of organs". Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine, stated "The exciting studies reported here are the first to demonstrate that non-viral gene delivery can be made cell-specific by controlling the nuclear entry of plasmid DNA, and as such, establishes a new paradigm for cell-selective gene delivery. Drs. Dean, Young, and Zimmer are to be congratulated on this ground-breaking study".
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Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
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In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
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The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
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Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
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The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
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