Scientists device new way limit gene transfer to specific tissues in animalsJune 23rd, 2008 - 3:30 pm ICT by ANI
Washington, June 23 (ANI): American scientists have devised a technique to limit gene transfer and expression to specific tissues in animals.
Researchers from Northwestern University and Texas A & M University say that a previous study, conducted to determine how plasmids enter the nuclei of non-dividing cells, had unveiled 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.
They say that their current study shows that such restrictions 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.
Writing about their work in the journal Experimental Biology and Medicine, the researchers also have revealed that 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.
According to them, their study 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.
The researchers are of the opinion that gene therapy may represent an important alternative for the treatment and prevention of vascular smooth muscle proliferative diseases, including atherosclerosis and restenosis, which are among the leading causes of morbidity in the US.
A number of gene delivery systems for use on the arterial wall are being studied these days, but as yet their low efficiency in gene transfer and lack of cell-specific targeting and expression are major limitations.
“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,” says Dr. David Dean, an expert at the Department of Medicine at Northwestern University.
The researcher has revealed that his teams objective is to design more effective gene therapy vectors for use in the vasculature by understanding the molecular mechanisms whereby DNA and DNA-protein complexes are actively transported into the nucleus.
“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,” says Dr. Warren Zimmer of Texas A & M University.
Dr. Dean adds: “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, says: “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.” (ANI)