Journal or Publishing Institution: Regulatory Toxicology and Pharmacology
Study: http://www.sciencedirect.com/science/article/pii/S0273230015000227
Author(s): Heinemann, J.A., Agapito-Tenfen, S.Z. and Kurenbach, B.
Article Type: Journal Publication
Record ID: 983
Abstract: The conclusion of a 28-day study feeding mice double-stranded (ds)RNA published in this journal was that: “toxicity and target gene expression as surrogate measures of any biologically meaningful absorption/biodistribution or activity of ingested dsRNA. This is because any relevant impact of an absorbed nucleic acid on gene expression (e.g., ability to reach a target and trigger on-target or off-target gene suppression) would manifest itself as a physiological impact”. (Petrick et al., 2015) The data provided, however, fall short of demonstrating that the test material and the test subjects were appropriate for these objectives. The four, among other, critical issues are: (1) the lack of a verifiable and replicated effect of the siRNAs on target mRNA; (2) lack of appropriate endpoint measurement for RNAi, specifically, protein level changes in exposed tissues or animals or expected phenotypic changes; (3) limited ways animals were exposed; and (4) substitution of mice for rats and relaxation of weight variation limits as specified by OECD Test Guideline 407.
Keywords: RNAi, dsRNA, Risk assessment
Citation: Heinemann, J.A., Agapito-Tenfen, S.Z. and Kurenbach, B., 2015. Response to” A 28-day oral toxicity evaluation of small interfering RNAs and a long double-stranded RNA targeting vacuolar ATPase in mice.” Regulatory Toxicology and Pharmacology: RTP, 71(3), pp.599-600.