Adeno-Associated Virus Inverted Terminal Repeats Improve Neuronal Transgene Expression Mediated by Baculoviral Vectors in Rat Brain

Abstract

Baculoviral vectors can transduce neurons in the CNS but mediate only transient expression of transgenes. We have developed a new baculoviral vector in which the inverted terminal repeats (ITRs) of adeno-associated virus are used to flank a luciferase reporter gene cassette harboring a neuron-specific promoter. When tested in rat brain, the new viral vector was able to provide transgene expression for at least 90 days. Immunohistological analysis demonstrated that ITR flanking did not affect the cellular preference of the neuronal promoter in the context of baculovirus. These findings establish an effective way to engineer baculoviral vectors in order to achieve sustained expression of a functional gene for gene therapy for neurodegenerative disorders and physiological studies of neurons.