Author
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WITWER, KENNETH - Johns Hopkins University |
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YANG, JIAN - Children'S Nutrition Research Center (CNRC) |
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FARMER, LISA - Children'S Nutrition Research Center (CNRC) |
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MCALEXANDER, MELISSA - Johns Hopkins University |
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BISSIG, KARL-DIMITER - Baylor College Of Medicine |
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KONGCHAN, NATEE - Baylor College Of Medicine |
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NEILSON, JOEL - Baylor College Of Medicine |
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HIRSCHI, KENDAL - Children'S Nutrition Research Center (CNRC) |
Submitted to: Keystone Symposia
Publication Type: Abstract Only Publication Acceptance Date: 12/11/2013 Publication Date: 1/31/2014 Citation: Witwer, K.W., Yang, J., Farmer, L.M., Mcalexander, M.A., Bissig, K., Kongchan, N., Neilson, J., Hirschi, K.D. 2014. Revisiting absorption of dietary plant-based miRNAs [abstract]. The Keystone Symposia on Molecular and Cellular Biology: Accelerating Life Science Discovery; RNA Silencing, January 31-February 5, 2014, Seattle, Washington, 1066, p 62. Interpretive Summary: Technical Abstract: We are continuing to test the hypothesis that consumption of genetic information in plant-based foods can modulate animal metabolism. Several studies (1,2,3) have failed to replicate the finding (4) that a rice miRNA survives digestion, enters circulation in copy numbers rivaling endogenous RNAs, and modulates gene expression in the liver. While we have also failed to reproduce these findings, it remains possible that uptake and clearance of exogenous RNAs is modulated during certain medical conditions or by intake of substances including alcohol and traditional herbal remedies. Here, we describe a dietary regime that appears to allow some plant-based miRNAs to be detected in sera of the consuming mammals. We fed 8- to 10-week-old mice for multiple days a diet enriched with a specific herb and then gavage-fed these same mice a concentrated herbal tea extract. Using RT-qPCR, we demonstrated circulating herbal miRNA for several hours afer gavage feeding. Droplet digital PCR results suggested that this detection was specific. Finally, we described an adeno-based "sensor" system for in vivo testing of the action of the orally ingested RNA in the presence or absence of uptake- or clearance-modulating factors. This system involves non-invasive imaging of mice following dietary intake. To further assay phenotypes, we have made transgenic plants expressing validated siRNAs that target clotting factors V and VII, which are produced in hepatocytes and have a short half-life (3-12 hours) conducive to rapid response monitoring. These studies may establish a mechanism that could lead to tailored plant-based diets as economical and novel therapies. |