Although small animals such as mice and rats are frequently used to test small molecule drugs, they may not be suitable for testing RNA-based therapies. Because human and rodent genetic sequences can diverge, a functional small RNA in rodents may not be valid in humans, especially for those that target gene promoter sequences. In Sildenafil Mesylate contrast, non-human primates share almost identical genome sequences with human and are more ideal for testing genetic therapies. In fact, non-human primate disease models are often used to test preclinical safety and efficacy of vector-based gene therapy and for testing systematic delivery of RNAi-based therapeutics. So far, RNAa has only been demonstrated in human cells and is unknown whether it is conserved in other mammals. In the present study, wereplicate and Irinotecan hydrochloride identify newexamples of RNAa innon-human primate, mouse, and rat cells. We show that saRNAs derived from human sequences have RNAa activity in non-human primate cells. This suggests non-human primate disease models may have clinical relevance in validating RNAa-based drugs. We also demonstrate RNAa in other mammalian species by testing saRNAs derived from mouse and rat sequence in rodent cells. Our findings reveal that RNAa is prevalent in mammalian species other than human with most of the genes tested being readily activated by saRNAs. RNA activation is a newly discovered mechanism of small RNA-directed gene activation originally identified in human cell lines. It offers similar benefits as RNAi by utilizing small dsRNAs, while representing a new method for gene overexpression. As the momentum of RNAa increases within the scientific community, it is important to determine if this phenomenon is conserved in other mammalian species. Within this study, we replicate and identify new examples of RNAa in non-human primates, mouse, and rat cells. This not only demonstrates conservation of RNAa, but also reveals its potential application in animal studies other than human. In fact, during the preparation of this manuscript, it was shown that lentiviral-based delivery of shRNAs could activate VEGF expression by targeting promoter sequences in an ischemic mouse model.