1. ¹Institute of Bioengineering and Nanotechnology, Singapore 138669
2. ²Department of Biological Sciences, National University of Singapore, Singapore 119260

Correspondence: Shu Wang, Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos No. 04-01, Singapore 138669. Fax: 65-6478 9083. E-mail: swang@ibn.a-star.edu.sg

Received 8 July 2004; Accepted 23 August 2004.

Abstract

Targeted gene delivery to neurons is crucial to effective gene therapy of neurodegenerative diseases. Several types of viral gene vectors may target neurons through retrograde axonal transport to somas of projection neurons after viral internalization at axon terminal fields. In this report we demonstrate for the first time that recombinant baculovirus vectors could migrate by axonal transport to cell bodies, resulting in transgene expression in projection neurons. After stereotaxic injection of Cy3-labeled baculovirus vectors into the rat striatum, retrograde axonal transport of the baculovirus vectors was observed along the corticostriatal pathway and nigrostriatal pathway. Furthermore, after intra-vitreous body injection, anterograde axonal transport and transsynaptic transport of the virus particles were observed in defined connections of the visual system, from the retina to the optic nerve, the lateral geniculate body, the superior colliculus, and the primary visual cortex. PCR analysis confirmed the existence of transported viral DNA in the tissue samples collected from projection fields. Driven by a neuron-specific promoter, transgene expression from the recombinant baculovirus vectors was detectable in target regions remote from injection sites. The attributes of baculovirus vectors in the bidirectional axonal transport and transneuronal transport in neural circuits of the central nervous system could be utilized for targeted gene delivery.