Iron storage molecule in the cell can serve as advanced tool for mapping gene ex

[Guest guest]

Iron storage molecule in the cell can serve as advanced tool for

mapping gene expression

10 May 2005 Medical News Today

New findings show an iron storage molecule in the cell can serve as

an advanced tool for mapping gene expression. Future gene therapy may

use a technique in which non-invasive magnetic resonance imaging

(MRI) is used to track this molecule. The results of this research,

conducted by Prof. Michal Neeman of the Weizmann Institute's

Biological Regulation Department, were published in the research

journal Neoplasia.

Neeman, together with Dr. Batya Cohen of the Institute's Molecular

Genetics Department, developed the capacity of the iron-bearing

ferritin molecule to serve as a sort of gene " spy " by making genetic

modifications to cells. This approach rendered ferritin sensitive to

tetracycline (TET), a common antibiotic, so that when TET is present,

the ferritin is " off " and when TET is absent, ferritin is " on. " Tumor

cells with modified ferritin were inserted into living mice and then

tracked with MRI. The researchers hampered the expression of ferritin

in the inserted cells through the administration of TET. When they

stopped the TET, the " switch " turned on, triggering ferritin

molecules to increase their numbers, thereby causing an increase in

iron uptake within the tumor cells. The contrast between the iron

content in these and in the normal surrounding cells showed up in the

MRI (which is sensitive to magnetic particles such as iron),

effectively identifying the genetically modified cells.

This method grew out of a joint vision that originated 10 years ago

in collaboration with the late Dr. Yoav Citri. Ferritin's advantage

is that it is visible in MRI without the need for an additional

contrast material. This technique has far-reaching implications for

monitoring the progress of gene therapy, such as that used to

reactivate the body's production of insulin in the treatment of

diabetes, because the genes can be " tagged " prior to injection.

Therapeutic genes can then be tracked by MRI to ensure the target is

reached and the desired activations occur. Prof. Neeman: " The use of

ferritin as a reporter gene would be particularly beneficial in those

cases where administration of contrast material is compromised by

barriers, including embryonic development and the central nervous

system. "

Prof. Michal Neeman's research is supported by the M.D. Moross

Institute for Cancer Research; the Willner Family Center for Vascular

Biology; the Women's Health Research Center; the Mark Family

Foundation; and Mr. and Mrs. Meadow, Beverly Hills, CA.