Recently we reported that site-specific enzymatic incorporation of a quencher attached to diGTP can be used to create a new and highly sensitive real-time PCR system (26 ) . Polymerase incorporation of labels only at sites where expanded genetic alphabet bases are positioned will also have other uses, such as 3Ј end labeling. Polymerase incorporation of EraCodes within PCR amplicons has now also been reported (27 ) . The EraCode system that uses additional nonnatural base pairing may have advantages over other DNA-based molecular recognition systems (28 -30 ) . These short DNA codes are simple to produce, specifically hybridize at room temperature, do not require wash steps, can be amplified with standard polymerases, and do not cross-hybridize with natural DNA. Taken together, we believe that the expansion of the genetic alphabet is a true paradigm shift to the ways molecular diagnostics will be developed in the future. Antisense-induced ribosomal frameshifting Programmed ribosomal frameshifting provides a mechanism to decode information located in two overlapping reading frames by diverting a proportion of translating ribosomes into a second open reading frame (ORF). The result is the production of two proteins: the product of standard translation from ORF1 and an ORF1–ORF2 fusion protein. Such programmed frameshifting is commonly utilized as a gene expression mechanism in viruses that infect eukaryotic cells and in a subset of cellular genes. RNA secondary structures, consisting of pseudoknots or stem–loops, located downstream of the shift site often act as cis-stimulators of frameshifting. Here, we demonstrate for the first time that antisense oligonucleotides can functionally mimic these RNA structures to induce +1 ribosomal frameshifting when annealed downstream of the frameshift site, UCC UGA. Antisense-induced shifting of the ribosome into the +1 reading frame is highly efficient in both rabbit reticulocyte lysate translation reactions and in cultured mammalian cells. The efficiency of antisense-induced frameshifting at this site is responsive to the sequence context 5′ of the shift site and to polyamine levels. The standard triplet readout of the genetic code can be reprogrammed by signals in the mRNA to induce ribosomal frameshifting [reviewed in (1) (2) (3) ]. Generally, the resulting trans-frame protein product is functional and may in some cases be expressed in equal amounts to the product of standard translation. This elaboration of the genetic code (4, 5) demonstrates versatility in decoding.