- Cancer Biology & Biomarkers
- Chromatography & Mass Spectrometry
- Contract Research, Clinical Trials and Outsourcing
- Drug Discovery
- Drug Targets
- Flow Cytometry
- Informatics & Lab Automation
- Ingredients, Excipients and Dosages
- Microbiology & RMMs
- NIR, PAT & QbD
- Raman Spectroscopy
- Screening, Assays & High-Content Analysis
- Thermal Processing
- Events & Workshops
Pål Sætrom - Articles and news items
Genomics, Issue 5 2011 / 19 October 2011 / Marie Lundbæk, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology and Pål Sætrom, Department of Cancer Research and Molecular Medicine & Department of Computer and Information Science, Norwegian University of Science and Technology
RNA interference (RNAi) is now a standard tool in molecular biology. Short interfering RNAs (siRNAs) for knocking down your favourite human gene are only a couple of mouse-clicks away at your favourite reagent supplier’s website. Moreover, in contrast to initial attempts at siRNA design, these siRNAs usually give potent target gene knockdown. Nevertheless, siRNAs are not always a cure-all; therapeutic settings often require combinatorial treatments and may necessitate effects that are incompatible with standard siRNAs, such as targeted gene up-regulation. Here, we review the features of standard siRNAs before describing three unconventional but therapeutically relevant approaches to RNAi: multi-targeting siRNAs, immunostimulatory siRNAs, and transcription-modulating siRNAs.
Fire and Mello coined the term RNA interference when they discovered that long doublestranded RNAs cause sequence specific gene inhibition in worms1,2. The enzyme Dicer processes such long double-stranded RNAs into short double-stranded ~22 nt duplexes with 2 nt 3’ overhangs – the siRNAs. Argonaute 2 (Ago2) then incorporates one of the siRNA strands and uses the strand as a guide to bind and cleave single-stranded RNAs such as messenger RNAs (mRNAs).
For plants and invertebrates, RNA interference is firmly established as an important antiviral mechanism. Even before Fire, Mello, and co-workers described RNA interference (RNAi) in worms in 19981 it was becoming clear that plants have an RNA-dependent pathway that protects against viral infections2. The pathway, then termed post-transcriptional gene silencing (PTGS), helps plants like tobacco recover from initial viral infections and ensures that plants are protected from subsequent infections from the same or similar viral strains3. Subsequent studies have revealed that plant PTGS and Fire and Mello’s RNAi are identical – the triggers are short RNAs derived from long double-stranded RNAs (dsRNA)4. Incorporated into the RNA-induced silencing complex (RISC), RISC cleaves transcripts like viral messenger RNAs (mRNAs) with antisense complementary to the short RNAs.
ABB Analytical Measurement ACD/Labs ADInstruments Ltd Advanced Analytical Technologies GmbH Analytik Jena AG Astell Scientific Ltd Bibby Scientific Limited Bio-Rad Laboratories BioNavis Ltd Biopharma Group Black Swan Analysis Limited Charles Ischi AG | Kraemer Elektronik Cherwell Laboratories CI Precision Cobalt Light Systems Coulter Partners CPC Biotech srl Dassault Systèmes BIOVIA DiscoverX Edinburgh Instruments Enterprise System Partners (ESP) EUROGENTEC F.P.S. Food and Pharma Systems Srl IDBS JEOL Europe L.B. Bohle Maschinen + Verfahren GmbH Lab M Ltd. LabWare Linkam Scientific Instruments Limited Molins Technologies Multicore Dynamics Ltd Nanosurf New England Biolabs, Inc. Panasonic Biomedical Sales Europe B.V. PerkinElmer Inc ReAgent Russell Finex Limited Source BioScience Takara Clontech Tornado Spectral Systems Tuttnauer Watson-Marlow Fluid Technology Group Wickham Laboratories Limited Xylem Analytics YMC Europe GmbH Yusen Logistics