Philip Liu
The AA Martinos Center for Biomedical Imaging, Department of Radiology, Mass General Hospital and the Harvard Medical School, Massachusetts, USA
Gene replacement has been proposed to improve neurological disorders. However, the efficacies are less than expected, perhaps due to less than optimal window of delivery and a lack of effective tracking of its distribution for evaluation. Here, we demonstrated effective delivery of cDNA encoding human granulocyte colony stimulating factor (G-CSF) protein in a selfcomplementary AAV2-CMV-hG-CSF as eye drops to mice after cerebral ischemia. Moreover, we tracked the expression of exogenous human G-CSF mRNA in living mouse brains using target-guided MRI. In supporting the function of stimulating vessel growth by G-CSF in the literature, we found eye drop delivery of G-CSF cDNA after cerebral ischemia reduced mortality, brain damage and neurological deficits and elevated global neurogenesis. The fact that eye drop is effective as a delivery route suggests that this route of delivery is translatable to emergency medicine for acute neurological disorders.