2011
DOI: 10.1093/bfgp/elr013
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Targeting genes in living mammals by RNA interference

Abstract: More than a decade has passed since the discovery of RNA interference (RNAi), an eukaryotic sequence-specific degradation of mRNA induced by complementary double-stranded RNA (dsRNA). RNAi became a common tool for controlled down-regulation of gene expression in cultured cells, as well as in various model organisms. This review summarizes RNAi-based tools for silencing genes in living mammals, which include: (i) transgenic RNAi strategies, where RNAi is triggered by a transgene transmitted through the germline… Show more

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Cited by 12 publications
(13 citation statements)
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“…The constitutive expression of certain amiRNA sequences that leads to embryonic lethality can eventually result in unavailability of a model for further studies 24 25 . A conditional expression strategy offers the best solution in such cases to generate a viable model.…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…The constitutive expression of certain amiRNA sequences that leads to embryonic lethality can eventually result in unavailability of a model for further studies 24 25 . A conditional expression strategy offers the best solution in such cases to generate a viable model.…”
Section: Resultsmentioning
confidence: 99%
“…To overcome the limitations associated with constitutive knockdown, such as lack of tissue-specificity or lethality due to RNAi, conditional approaches using Cre- lox P or inducible RNAi using tetracycline have been utilized 24 25 . In a Cre- lox P-based conditional RNAi approach, to prevent generation of constitutively active shRNA, lox P-flanked stuffer sequences were inserted into the shRNA loop or between the promoter and the shRNA 24 25 . In this case, RNAi is induced after Cre-mediated excision of stuffer sequence from the cassette.…”
Section: Discussionmentioning
confidence: 99%
“…siRNAs, approximately 21-nucleotide long, are produced in the cell from longer double-stranded RNAs or can be synthesised from small hairpin RNAs (shRNAs) transcribed from genetic constructs produced in the laboratory and introduced into the cells. RNAi has been used for the functional knockdown of specific proteins in several experimental systems, from cultured cells [1] to complete organisms, including mammals [2]. Typically, knockdown transgenic animals are produced by the introduction of the RNAi construct in the cells by lentiviral vectors or by pronuclear microinjection of one-cell embryos.…”
Section: Introductionmentioning
confidence: 99%
“…Typically, knockdown transgenic animals are produced by the introduction of the RNAi construct in the cells by lentiviral vectors or by pronuclear microinjection of one-cell embryos. It is also possible to generate knockdown animals from genetically modified ES cells [3]; for a review about the application of this technology to living mammals, see [2]. …”
Section: Introductionmentioning
confidence: 99%
“…The use of RNA interference (RNAi) technology has proven to be a very useful tool in disease modelling in mammalian systems [5]. The use of different promoters has allowed for tissue-specific expression of miRNAs, therefore restricting gene knockdown to targeted areas/organs, and also conditional knockdown with the use of Tet-on promoters (the Cre/loxP system is used in mice) [6].…”
Section: Introductionmentioning
confidence: 99%