Bioanalytical Community

Since discovered in the late 1990s, small-interfering RNA (siRNA) has become one of the frontiers in human healthcare research. siRNA drugs have opened novel avenues towards innovative therapies for many diseases that are not easily/readily targetable using conventional drug discovery approaches. 

In LC-MS bioanalysis of siRNAs, understandably, both antisense strand (AS) and sense strand (SS) need to be quantified and measuring AS is generally much more meaningful than SS. In case where SS is measured but data are not to be used for decision making or regulatory submission, how the SS data should be handled (e.g., listed for reference only or not reported)? On the other hand, when developing combo assay (both AS and SS in one method) in support of regulated studies, the assay generally needs to be fully validated for AS, will fit-for-purpose assay qualification be sufficient for SS? Lastly, if available data show that measurement of SS does not add any value to the respective project, do we still need to implement the 'validated/qualified combo assay' in support of subsequent preclinical and/or clinical studies?

Looking forward to hearing your feedback. Thx

Hi Wenkui,

Any results to share? I think on your Linkedin post it looks like >90% said both. 

Since discovered in the late 1990s, small-interfering RNA (siRNA) has become one of the frontiers in human healthcare research. siRNA drugs have opened novel avenues towards innovative therapies for many diseases that are not easily/readily targetable using conventional drug discovery approaches. 

In LC-MS bioanalysis of siRNAs, understandably, both antisense strand (AS) and sense strand (SS) need to be quantified and measuring AS is generally much more meaningful than SS. In case where SS is measured but data are not to be used for decision making or regulatory submission, how the SS data should be handled (e.g., listed for reference only or not reported)? On the other hand, when developing combo assay (both AS and SS in one method) in support of regulated studies, the assay generally needs to be fully validated for AS, will fit-for-purpose assay qualification be sufficient for SS? Lastly, if available data show that measurement of SS does not add any value to the respective project, do we still need to implement the 'validated/qualified combo assay' in support of subsequent preclinical and/or clinical studies?

Looking forward to hearing your feedback. Thx