Rutgers scientists have developed compositions of single-stranded oligonucleotides that inhibit RNA biosynthesis by a novel mechanism of action. This enables the development of highly efficient silencing agents that have shown unprecedented inhibitory levels in vitro. The U1 adaptor consists of two parts, a target-gene binding domain and a U’1 domain that attracts and inhibits the cellular splicing apparatus. By combining both capabilities in the same molecule, the U1 adaptor can inhibit the pre-mRNA maturation step of polyA tail addition. Further, the domains of the oligonucleotide are independent so transcript binding and splicing inhibition can be independently optimized and adapted to a wide array of genes.