Open AccessInducible and reversible breaching of the blood brain barrier by RNAi
Author(s) -
Rossi John J.
Publication year - 2011
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.1002/emmm.201100132
Subject(s) - rna interference , gene knockdown , biology , small interfering rna , gene silencing , gene , gene expression , messenger rna , microbiology and biotechnology , rna , computational biology , genetics
Abstract Sequence‐specific knockdown of gene expression is a goal that has been long sought by both basic and clinical investigators. In this regard, the discovery of RNA interference (RNAi) in Caenorhabditis elegans was immediately recognized as a potential breakthrough for studying gene function (Fire et al, 1998). These findings demonstrated that double‐stranded (ds)RNAs are triggers for sequence‐specific, post‐transcriptional gene silencing via targeted degradation of messenger RNAs harbouring a complementary sequence to one of the two strands. Initially, it was thought that such post‐transcriptional regulation of gene expression could not be achieved in mammalian systems due to the strong induction of interferon by dsRNAs. This potential restriction was short lived with the demonstration that endonuclease processed dsRNAs of 21–25 nucleotides in length, designated small interfering RNAs (siRNAs), were able to elicit sequence‐specific degradation of mRNAs in mammalian cells without triggering interferon responses (Elbashir et al, 2001). These findings provided a huge impetus to develop RNAi as a therapeutic modality. The dream to selectively block the expression of deleterious proteins and treat formerly non‐drugable diseases led to the rapid establishment of new biotech companies and branches of major pharmaceutical companies devoted to RNAi therapeutics. See related article in EMBO Mol Med (Campbell et al. (2011) EMBO Mol Med 3: 228–238 )