provide promise that similar uses can be leveraged in toxicological sciences. Despite these qualities, there remain significant technical challenges to reducing variability in measurements and to increasing our confidence in the application of these biomarkers. A standardization of protocols and reporting efforts analogous to the Transcriptomics Reporting Framework (Gant et al. 2017), and large-scale database efforts to categorize EV contents relating to source cells will be important for biomarker identification and for linking biofluid measured miRNAs to specific tissues, cells, and biological effects (see exRNA Atlas: Murillo et al. 2019). These and other concerted efforts will ultimately lead to a consistent and widespread use of miRNAs in regulatory and toxicological sciences.
Acknowledgements
The authors wish to thank Drs. Sheau-Fung Thai, Chris Corton, Sid Hunter and Kimberly Slentz-Kesler for their critical reviews of this manuscript. This manuscript has been reviewed by the US Environmental Protection Agency and approved for publication. Approval does not signify that the contents reflect the views of the Agency, nor does the mentioning of trade names or commercial products constitute endorsement or recommendation of use.
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