Novel Method for Monitoring RNAi Activity in Blood Samples

Novel Method for Monitoring RNAi Activity in Blood Samples

Our scientists discovered a new method for monitoring RNAi activity in blood samples.  The results were presented at the Keystone Gene Silencing by small RNAs symposium (Vancouver, February 7-12).  This new method, circulating extracellular RNA detection (cERD), allows quantitative measurement of tissue-specific mRNA silencing from biological fluids including blood and cerebrospinal fluid (CSF).

Based on analysis of serum samples, mRNAs appear to circulate in blood via exosomes, a newly discovered class of cell-derived particles.  The cERD method allows analysis of all circulating RNA, whether or not it is associated with exosomes.

New pre-clinical results demonstrate that tissue-specific mRNAs can be detected in blood and CSF in a non-invasive manner.

  • Administration of RNAi therapeutics targeting two tissue mRNA, TTR and Tmprss6, resulted in dose-dependent silencing — measured in tissue samples, and blood-derived mRNA–measured by the cERD method.  Both onset and duration of mRNA silencing were found to be closely matched between tissue and blood-derived mRNA.  Pre-clinical results were confirmed in a variety of animal models.
  • Administration of RNAi therapeutics targeting alpha-synuclein in the CNS resulted in silencing the target gene in both tissue and CSF-derived mRNA– measured by the cERD method.

The cERD method was also successfully applied to monitor activity of microRNA therapeutics and gene therapy vectors.

Research on the new cERD method was done in collaboration with Derrick Gibbings at the Swiss Federal Institute of Technology, Zurich.


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