Antisense Oligonucleotide Approach to Study NPY-Mediated Feeding Signal Transduction

Antisense oligodeoxynucleotides have been successfully employed to study the function of viral and cellular genes by sequence-specific inhibition. The antisense oligodeoxynucleotides are single-stranded, short, native, or chemically modified nucleotides that inhibit individual gene expression by selective complementary base pairing. These antisense compounds that inhibit gene expression can be grouped into two classes: (1) those leading to a reduction in target RNA levels, and (2) those that do not reduce target RNA levels. Inhibition of RNA function by antisense oligodeoxynucleotides without affecting RNA stability may be due to the disruption of RNA-protein or RNA-RNA interactions that are essential for RNA translation into protein synthesis. Translation arrest without destabilizing mRNA has been demonstrated in vitro using compounds targeted to the translation initiation site (1 ,2 ). Binding of antisense oligodeoxynucleotides to the AUG start codon can inhibit translation initiation by inhibiting ribosome assembly (3 ).