Is there experimental evidence that the potency of siRNAs is influenced by target accessibility and secondary structure?
• Target accessibility has long been established as an important factor for the potency of antisense oligonucleotides and trans-cleaving ribozymes. Recently, the importance of target structure and accessibility in determining the potency of siRNAs has been demonstrated, using a number of experimental approaches that include oligo library (Lee et al. 2002, Nat. Biotech., 20, 500-505; pp. 502, 503), oligo array (Bohula et al. 2003, J.Biol. Chem. 278, 15991-15997), antisense evaluation of accessibility (Far and Sczakiel (2003, Nucleic Acids Research, 31, 4417-4424) ), and by targeting the same sequence in both structured and unstructured sites (Vickers et al. 2003, J. Biol. Chem. 278, 7108-7188; p.7114, left column, top paragraph).
