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What is the difference between ON-TARGET, ON-TARGETplus, siSTABLE, and unmodified siRNA duplexes? When should I use the modified versions?

ON-TARGET siRNA duplexes are modified so that sense strand interactions with the RISC are impaired and interactions with the antisense (silencing) strand are favored. If you use our siDESIGN Center, it will indicate if this modification should be added based on your siRNA sequence. ON-TARGETplus siRNA incorporates the ON-TARGET modification plus an additional modification to improve specificity of antisense strand binding to its target. This modification is the most comprehensive for combating off-target effects. siSTABLE duplexes are modified to confer resistance to degradation by nucleases that can occur extracellularly or intracellularly. These duplexes should be considered for use when working with in vivo models or other systems that may expose the siRNA to a high nuclease environment. Unmodified siRNA duplexes do not carry any chemical modifications.