Co-expression of anti-NFkappaB RNA aptamers and siRNAs leads to maximal suppression of NFkappaB activity in mammalian cells

Nucleic Acids Research
Robert ChanP Shannon Pendergrast

Abstract

The specific down-regulation of gene expression in cells is a powerful method for elucidating a gene's function. A common method for suppressing gene expression is the elimination of mRNA by RNAi or antisense. Alternatively, oligonucleotide-derived aptamers have been used as protein-directed agents for the specific knock-down of both intracellular and extracellular protein activity. Protein-directed methods offer the advantage of more closely mimicking small molecule therapeutics' mechanism of activity. Furthermore, protein-directed methods may synergize with RNA-directed methods since the two methods attack gene expression at different levels. Here we have knocked down a well-characterized intracellular protein's activity, NFkappaB, by expressing either aptamers or small interfering RNAs (siRNAs). Both methods can diminish NFkappaB's activity to similar levels (from 29 to 64%). Interestingly, expression of both aptamers and siRNAs simultaneously, suppressed NFkappaB activity better than either method alone (up to 90%). These results demonstrate that the expression of intracellular aptamers is a viable alternative to siRNA knock-down. Furthermore, for the first time, we show that the use of aptamers and siRNA together can be th...Continue Reading

References

Jan 1, 1997·Gene Therapy·P D GoodD R Engelke
Mar 31, 1999·Proceedings of the National Academy of Sciences of the United States of America·M BlindM Famulok
Apr 26, 2001·Proceedings of the National Academy of Sciences of the United States of America·G MayerM Famulok
May 1, 2001·Biochemistry·L A Cassiday, L J Maher
Jul 28, 2001·Trends in Immunology·D A BleijsY van Kooyk
Aug 2, 2001·Proceedings of the National Academy of Sciences of the United States of America·N J CaplenR A Morgan
Oct 9, 2001·Chemistry & Biology·M FamulokG Mayer
May 1, 2002·Nature Biotechnology·Cynthia P PaulDavid R Engelke
Jul 12, 2002·Nature·Gregory J Hannon
Nov 5, 2002·Trends in Biotechnology·Michael Famulok, Sandeep Verma
Dec 26, 2002·The Journal of Biological Chemistry·Timothy A VickersBrenda F Baker
Jan 28, 2003·Drug Discovery Today·Petra BurgstallerMichael Blind
Jun 11, 2003·Nature Genetics·Alan J BridgeRichard Iggo
Aug 28, 2003·Nature Cell Biology·Carol A SledzBryan R G Williams
Oct 4, 2003·Nature Reviews. Drug Discovery·Mark A Lindsay
Feb 6, 2004·Proceedings of the National Academy of Sciences of the United States of America·Sunita GuptaVivek Mittal

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Citations

Aug 21, 2007·Nucleic Acids Research·Yong Seok ChoiSunjoo Jeong
Nov 27, 2010·Science·Stephanie J CullerChristina D Smolke
Sep 1, 2007·Expert Opinion on Drug Discovery·Aniela WochnerMartina Rimmele
Mar 31, 2009·Advanced Drug Delivery Reviews·Yu-Cheng TsengLeaf Huang
Apr 17, 2007·Advanced Drug Delivery Reviews·Lekha Dinesh Kumar, Alan R Clarke
Feb 7, 2007·Gene Therapy·N S Que-Gewirth, B A Sullenger
Mar 26, 2009·Angewandte Chemie·Günter Mayer
Aug 30, 2008·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Errol B De SouzaDinah W Y Sah
Aug 25, 2007·Chemical Reviews·Michael FamulokGünter Mayer

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Methods Mentioned

BETA
transfection
gene knock-out
PCR
in
Protein Assay
three-hybrid

Software Mentioned

BLAST

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