title: Noninvasive tracking of gene transcript and neuroprotection after gene therapy.
abstract: Gene therapy holds exceptional potential for translational medicine by improving the products of defective genes in diseases and/or providing necessary biologics from endogenous sources during recovery processes. However, validating methods for the delivery, distribution and expression of the exogenous genes from such therapy can generally not be applicable to monitor effects over the long term because they are invasive. We report here that human granulocyte colony-stimulating factor (hG-CSF) complimentary DNA (cDNA) encoded in self-complementary adeno-associated virus-type 2 adeno-associated virus, as delivered through eye drops at multiple time points after cerebral ischemia using bilateral carotid occlusion for 60 min (BCAO-60) led to significant reduction in mortality rates, cerebral atrophy and neurological deficits in C57black6 mice. Most importantly, we validated hG-CSF cDNA expression using translatable magnetic resonance imaging (MRI) in living brains. This noninvasive approach for monitoring exogenous gene expression in the brains has potential for great impact in the area of experimental gene therapy in animal models of heart attack, stroke, Alzheimer's dementia, Parkinson's disorder and amyotrophic lateral sclerosis, and the translation of such techniques to emergency medicine.
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and the Harvard Medical School, Charlestown, MA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Ren
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and the Harvard Medical School, Charlestown, MA, USA.
authors.forename: Y I
authors.initials: YI
authors.lastname: Chen
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and the Harvard Medical School, Charlestown, MA, USA.
authors.forename: C H
authors.initials: CH
authors.lastname: Liu
authors.affiliation: Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, USA.
authors.forename: P-C
authors.initials: PC
authors.lastname: Chen
authors.affiliation: Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, USA.
authors.forename: H
authors.initials: H
authors.lastname: Prentice
authors.affiliation: Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, USA.
authors.forename: J-Y
authors.initials: JY
authors.lastname: Wu
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and the Harvard Medical School, Charlestown, MA, USA.
authors.forename: P K
authors.initials: PK
authors.lastname: Liu
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000473:pathology / Q000628:therapy*; D054022:Cerebrum / Q000473:pathology; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000066829:Neuroprotection; D009883:Ophthalmic Solutions; D016716:PC12 Cells; D054735:Phosphorothioate Oligonucleotides / Q000235:genetics; D051381:Rats
chemical_list: D018076:DNA, Complementary; D009883:Ophthalmic Solutions; D054735:Phosphorothioate Oligonucleotides; D016179:Granulocyte Colony-Stimulating Factor