snoMEN®: a novel, highly efficient system for gene silencing
This novel vector system presents significant advantages over current technology: Allows for multiplex delivery of a pool of knockdown snoRNAs from a single vector. RNA polymerase II promoter, e.g. CMV, inducible promoters, is available. A single vector can be targeted to different sites in the same gene. A single vector can deliver knockdown of two or more different target genes simultaneously. The system can be used as a protein replacement vector for protein knock-in. The system can be used as a non-coding RNA knockΓÇôdown vector. Wide variety of delivery methods available.
Gene silencing technology such as RNA interference (RNAi) has immense potential in multiple areas such as target validation as well as the potential to form the basis of new therapeutics. As with all developing technologies, the techniques are not without their limitations ΓÇô opportunities remain for the development of novel approaches which can overcome current constraints.
Researchers at the University of Dundee have developed a novel vector system, based on human small nucleolar RNAs (snoRNAs), capable of targeted knockdown of one or more genes in mammalian cells. The system presents significant advantages over current technology: Allows for multiplex delivery of a pool of knockdown snoRNAs from a single vector. RNA polymerase II promoter, e.g. CMV, inducible promoters, is available. A single vector can be targeted to different sites in the same gene. A single vector can deliver knockdown of two or more different target genes simultaneously. The system can be used as a protein replacement vector for protein knock-in. The system can be used as a non-coding RNA knock–down vector. Wide variety of delivery methods available.SnoMEN® Vector SystemsnoRNAs comprise a family of nuclear RNAs present within the nucleoli of all eukaryotic cells and which function in the modification or processing of rRNA. There are two main classes of snoRNAs: the box C/D snoRNAs and the box H/ ACA snoRNA.Dundee researchers have identified a novel human box C/D snoRNA (HBII-180C) and demonstrated that a short, internal region within this snoRNA - termed the M box – can be manipulated to make it complementary to a target RNA sequence of choice. This modified snoRNA (M box-modified snoRNA) is capable of mediating gene knockdown. The snoMEN® system benefits from the fact that endogenous box C/D snoRNAs are highly abundant nuclear RNAs, efficiently processed from within introns of many different protein coding cellular pre-mRNAs. Mulitple M box-modified snoRNAs can be delivered simultaneously in a single multiplex vector transcript and expression can be controlled from a single promotor.Gene knockdown mediated by snoMEN® vector systemsGene specific knockdowns have been demonstrated for endogenous cellular proteins and for G/YFP-fusion proteins: Multiple snoRNAs can be expressed in one vector and targeted to different regions of RNA  The multiple snoRNAs can be targeted to different regions of the same target RNA; different RNA targets; or both. Multiplexed snoRNAs can simultaneously knock down multiple target genes
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