Inhibition of kinesin synthesis and rapid anterograde axonal transport in vivo by an antisense oligonucleotide

Abstract

Synthetic antisense oligonucleotides have been used to inhibit specific protein synthesis in vivo. Antisense oligonucleotides directed to kinesin heavy chain were injected into the vitreous of anesthetized rabbits in order to assess the effects on transport in the retinal ganglion cells whose axons form the optic nerve. The antisense oligonucleotide specifically inhibited retinal kinesin synthesis by 82 +/- 7% (n = 4). The rapid axonal transport of the membrane proteins into the optic nerve was concomitantly inhibited by 70 +/- 10% (n = 4). These results provide direct evidence for the specific role of kinesin in rapid anterograde transport in vivo and indicate the utility of antisense oligonucleotides to explore neuronal dynamics in a specific neuronal cell type in a living animal.