Role of Toll-like receptors in antisense and siRNA [corrected].
About 25 years ago, researchers first demonstrated that a short synthetic oligodeoxynucleotide, referred to as antisense, can inhibit replication of Rous sarcoma virus through hybridization to viral RNA. Since then, several hybridization-based oligonucleotide approaches have been developed to elucidate the functions of genes and their potential as therapeutic agents. Short-interfering (si) RNA is the most recent example. To effectively inhibit gene expression, an antisense or siRNA must be resistant to nucleases, be taken up efficiently by cells, hybridize efficiently with the target mRNA and activate selective degradation of the target mRNA or block its translation without causing undesirable side effects. However, both antisense and siRNA agents have been shown to exert non-target-related biological effects including immune stimulation. Do antisense and siRNA agents work as ligands for Toll-like receptors (TLRs), a family of pathogen-associated, molecular pattern recognition receptors?
Agrawal
Sudhir
S
Hybridon, Inc., 345 Vassar Street, Cambridge, Massachusetts 02139, USA. sagrawal@hybridon.com
Kandimalla
Ekambar R
ER
D002986:Clinical Trials as Topic; D020868:Gene Silencing; D018390:Gene Targeting / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000235:genetics*; D016372:RNA, Antisense / Q000008:administration & dosage* / Q000235:genetics*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors* / Q000235:genetics*; D051193:Toll-Like Receptors
D008562:Membrane Glycoproteins; D016372:RNA, Antisense; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors