(93q) Selection of Effective Antisense Oligonucleotides and Short Interfering Ribonucleic Acids
AIChE Annual Meeting
Monday, October 31, 2005 - 12:30pm to 4:00pm
Antisense technology has been recognized as a method to inhibit the expression of specific proteins and possesses great potential to treat diseases like AIDS, cancer and cardiovascular. Conceptual simplicity, inexpensive cost, speed and specificity have led to the use of antisense and siRNA technology. Antisense oligonucleotides (AS ODNs) used in the present study are chemically modified single stranded DNA molecules which selectively inhibit the expression of one gene in a human cell expressing thousands of other genes. They bind to the messenger RNA of target gene containing the complementary sequence, preventing its translation into the target (e.g., disease causing) protein. RNA interference (RNAi) is triggered by double stranded RNAs called short interfering RNAs that also induce selective gene silencing. The present project examines the action of AS ODNs and siRNA on GFP (green fluorescent protein) transfected Chinese Hamster Ovarian-K1 cells. Flow cytometry is used to measure quantitatively and on a cell population level the inhibition of GFP expression induced by AS ODN and siRNA. The results indicate a complex dependence of effectiveness on oligonucleotide type (AS ODN vs. siRNA),transfection protocol and time after delivery. The antisense and siRNA technologies have emerged as valid approaches to selectively modulate gene expression and their effective implementation during drug development can accelerate the path to clinic.