OVERVIEW
Gene action in brain cells regulates most activities in normal and disease conditions, including brain functions related to learning, stress response and psychiatric and neurologic disorders, as well as general medical disorders such as cardiovascular disease, stroke, and traumatic injury that change brain energy metabolism and blood flow. The great wealth of information on polymorphisms (small and insignificant variations in coding regions) in genes can be associated with neurological disorders such as Alzheimer’s disease and Parkinson’s disease. Most current studies suggest that regulatory regions of specific genes (and thus variation in gene activites) may more likely explain phenotypic variability among humans. Some propopse that chemical imbalance in the brain may change gene activities in neurons and cause abnormal synaptic firing, thereby impacting human mental health. Abnormal behavior of drug users in humans is believed to be related to abnormal gene activities. Our well-being may be a result of gene action by neural environment. Some such variations in gene activities occur globally, throughout the entire brain, while some, in a great many cases, affect only small numbers of cells. Still other changes in gene activation aid the brain in repairing damage caused by injury. We are interested in improving understanding of these changes in gene activities and hope that such greater understanding may be translated into gene targeting for therapeutic interventions that benefit patients.
However, procedures to detect gene activity in the brain are not routinely performed clinically because techniques to track gene changes rely on the use of biopsy or autopsy samples. Biopsy to obtain brain tissue severely limits the utility of these methods to monitoring gene activities in vivo, and often precludes longitudinal therapeutic evaluation altogether. Current methods using functional MRI techniques have provided a great wealth of information for mapping cell activation and structural mappings, but provide little information on genetic basis of such activities.
To answer these problems, we have developed patent-pending brain probes and non-invasive delivery method for Magnetic Resonance Imaging (MRI) that allow the use of imaging as a powerful and less invasive tool for in vivo detection of gene action in brain cells. Superparamagnetic iron oxide nanoparticles (SPION, a T2 susceptibility contrast agent in magnetic resonance, MR), are linked to a short nucleic acids with sequence complementary (antisense) to the target gene of interests in living brains (Liu et al, 2007 & 2008). Because the probes are charged molecules, they are taken up by brain cells along with SPION, and their retention and window of detection are determined by homology of the nucleic acid to cellular mRNA target. The presence of SPION with the probe in the living brain can then be imaged with MRI. This method can be applied to detect cells expressing specific mRNA in the brain that are involved in the activities of neurons or glia/astrocytes (a non-neuronal cell type that plays an important role in supporting the well-being of neurons). Other probes can be used to detect the formation of new blood vessels, stem cell activities, or scar formation during repair in the living brain in vivo. We expect that such probes have great potential for bedside application.
Four patent applications are pending approval from our work(US 60-303907)(US 60-959856)(US 60-959878) (US 60-962499).
