Design of antisense oligonucleotides and short interfering RNA duplexes (siRNA) targeted to BCL6 mRNA: towards rational drug development for specific lymphoma subsets.
Many algorithms based on computational analysis and thermodynamic parameters have been developed to predict the secondary structure of RNA. Still, many antisense oligodeoxynucleotides (AS ODNs), or siRNA molecules designed according to these predictions fail to silence the intended target, whereas other, not fulfilling those criteria prove highly active. We have developed a reliable mapping strategy, which allows us to predict the sites accessible for hybridization within target mRNA in vitro and in vivo. Our mapping experiments employed self-quenching reporter molecules (SQRMs) and were first carried out in a cell free system, and later confirmed in vivo.
Kalota
Anna
A
Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania, 421 Curie Blvd., Philadelphia, PA 19104, USA.
Opalinska
J B
JB
D015153:Blotting, Western / Q000379:methods; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics*; D015195:Drug Design; D015316:Genetic Therapy; D006801:Humans; D008223:Lymphoma / Q000235:genetics / Q000628:therapy; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics; D017421:Sequence Analysis
C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D016376:Oligonucleotides, Antisense; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger; D034741:RNA, Small Interfering