Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways

By D. Grimm, K. Streetz, C. Jopling, Theresa A. Storm, K. Pandey, C. Davis, P. Marion, F. Salazar, M. Kay. Nature, 2006

1,751 citations recorded by the source corpus.

View Paper: https://www.semanticscholar.org/paper/6cfe43fd5748b3382c143a5f8b8202c6e8cb5112

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Citations in the corpus

Artificial miRNAs mitigate shRNA-mediated toxicity in the brain: Implications for the therapeutic development of RNAi (2008, background): “Similar to our work, Grimm and colleagues (15) observed acute liver toxicity and mortality in mice after systemic shRNA delivery, which correlated with increased mature antisense RNA levels.”
A construct with fluorescent indicators for conditional expression of miRNA (2008, positive): “First, extremely high levels of shRNA expression should be avoided because such high levels of shRNA can induce non-specific toxicity [17].”
microRNAs in cancer (2013, background): “Beyond the RISC saturation effects described by Grimm and coworkers (148), there is the potential to induce unwanted effects when novel miRNAs are introduced into a cell.”
RNA interference in the clinic: challenges and future directions (2010, background): “Additionally, other investigators have shown that the high-level expression of short hairpin RNAs in the livers of mice overwhelmed the hepatic RNAi processing machinery, causing hepatic failure and deat”
The promises and pitfalls of RNA-interference-based therapeutics (2009, neutral): “Exogenously introduced dsRNA sequences can sequester components that make up the cellular machinery involved in gene silencing (see page 396 ), thereby reducing the accessibility of the machinery to a class of small RNAs known as microRNAs (miRNAs) that are entering the natural cellular pathwa”
RNAi therapeutics: a potential new class of pharmaceutical drugs (2006, background): “Although viral delivery provides the potential advantage that a single administration could lead to durable down-modulation of the targeted pathological protein, a major risk was highlighted recently 81 .”
The neuronal microRNA system (2006, background): “Recent data suggest that exogenous siRNAs can overwhelm miRNA processin”
Mammalian microRNAs: experimental evaluation of novel and previously annotated genes. (2010, background): “The level of mmu-miR-1224, an annotated mirtronic miRNA (Berezikov et al. 2007), increased in the presence of TNdrosha, as expected if this pre-miRNA had more access to Exportin-5 and Dicer when the canonical pre-miRNAs were reduced (Grimm et al. 2006).”
MicroRNAs en route to the clinic: progress in validating and targeting microRNAs for cancer therapy (2011, positive): “Previous reports suggest that the functions of two key miRNA silencing components, exportin 5 and Argonaute 2, are diminished when miRNA or siRNA levels are elevate”