New gene imaging technique peers into living tissue

CMU scientists, in collaboration with the Pittsburgh Nuclear Magnetic Research Center for Biomedical Research, have developed new magnetic resonance imaging (MRI) technology that will allow doctors and scientists to visualize the expression of specific genes in live tissue. This is the first time technology is under development that will allow scientists to monitor gene expression in live organisms, without having to sacrifice the organism.
?Our new MRI technology can be used in a variety of applications,? says Dr. Eric Ahrens, assistant professor of biological sciences in the Mellon College of Science at Carnegie Mellon. ?It can be used to specifically show if initial conditions and locations of gene delivery were as expected.?
Ahrens manipulated mammalian cells to make them produce their own contrast agent, a substance that will allow a particular tissue to be more visible to an MRI scan. He then inserted the gene that produces ferritin, a non-toxic protein that binds iron, into the cells. This metalloprotein acts like a nano-magnet, causing the nearby protons to give off a distinctly different signal, which is detectable to the MRI.
Ahrens? use of ferritin as a contrast agent is similar to the use of green fluorescent protein (GFP) in the detection of gene expression, but ferritin can be used in in vivo applications (those involving live subjects), allowing full scale, high resolution imaging of the gene of interest.
?[Ahrens] is able to detect protein in living organisms without having to sacrifice the animal. That?s the beauty of it, because in a sense it?s non-invasive,? says Dr. Danith Ly, an assistant professor of chemistry at CMU.
The new gene imaging technology allows for the detection of any given protein at any given time. The technology leaves a wide range of possible applications, including many for therapeutic gene delivery research.
Ferritin, when attached to a specific gene, is delivered to specific tissue in an organism via modified viruses that can?t replicate. This MRI technology proves a convenient method of monitoring the pathway of the gene under examination, to make sure it ends up in the correct places within the body.
?This is a platform technology ? it can be adapted for use in many cell types and for cell therapies, and can even eventually be used in humans,? says Mangala Srinivas, a doctoral student in Ahrens? lab.
Ferritin produces a natural protein and is non-toxic, allowing cells to readily take it up. Fusing ferritin to a specific gene, however, may prove detrimental to that gene?s natural expression and function in cells. This has been the case in many molecular markers used to detect genetic activity in the past. Other obstacles to using this new gene imaging technology will vary depending on the specific application. Only time will tell if the new technology will have a future in the research world; until scientists apply it in pre-clinical trials, they will be unable to predict all potential problems.
Dr. Ahrens applied his unique background in physics to the development of this new gene imaging technology. Ahrens received both his bachelors and PhD in physics, switching into the field of biology as a postdoctoral researcher at Caltech. His previous work in the field of physics includes NMR and superconductors.
Dr. Ahrens started working for CMU in 2000, and quickly became interested in MRI research. Switching into the field of molecular biology, he was able to apply his prior knowledge of spin physics to his biological research. Ahrens? diverse educational background has allowed him to excel in a field where expertise in physics is not the norm. ?I was able to apply my expertise across the disciplines, which if you look in the past is often the case with scientific breakthroughs,? says Dr. Ahrens.
?Ahrens? work is a breakthrough in biosensor detections,? says Ly, who works in the chemistry department but whose research on gene delivery tools extends beyond the barriers of disciples and into molecular biology and therapeutic research. ?This is a real biomedical application with great potential.?