INHIBITION OF KINESIN SYNTHESIS AND RAPID ANTEROGRADE AXONAL-TRANSPORT IN-VIVO BY AN ANTISENSE OLIGONUCLEOTIDE

Synthetic antisense oligonucleotides have been used to inhibit specifi c protein synthesis in vivo. Antisense oligonucleotides directed to ki nesin heavy chain were injected into the vitreous of anesthetized rabb its in order to assess the effects on transport in the retinal ganglio n cells whose axons form the optic nerve. The antisense oligonucleotid e 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 ant erograde transport in vivo and indicate the utility of antisense oligo nucleotides to explore neuronal dynamics in a specific neuronal cell t ype in a living animal.