We describe a gene silencing method that employs a mechanism of action distinct 
from those of antisense and RNA interference. U1 Adaptors are bifunctional 
oligonucleotides with a 'target domain' complementary to a site in the target 
gene's terminal exon and a 'U1 domain' that binds to the U1 small nuclear RNA 
component of the U1 small nuclear ribonucleoprotein (U1 snRNP) splicing factor. 
Tethering of U1 snRNP to the target pre-mRNA inhibits poly(A)-tail addition, 
causing degradation of that RNA species in the nucleus. U1 Adaptors can inhibit 
both endogenous and reporter genes in a sequence-specific manner. Comparison of 
U1 Adaptors with small interfering RNA (siRNA) using a genome-wide microarray 
analysis indicates that U1 Adaptors have limited off-target effects and no 
detectable adverse effects on splicing. Further, targeting the same gene either 
with multiple U1 Adaptors or with a U1 Adaptor and siRNA strongly enhances gene 
silencing.