Modulation of the efficiency of a siRNA directed against MDR1 expression in MCF7-R cells when combined with a second siRNA.

Effective silencing of MDR1, one of the genes involved in the multidrug resistance phenotype, can be achieved by the use of an efficient siRNA transfected into the doxorubicin-selected MCF7-R human cell line, alone or combined with a moderately efficient siRNA. On the contrary, there is no MDR1 silencing when it is co-transfected with a control siRNA that does not target the human genome. This results from the limited amount of RISC (RNA-Induced Silencing Complex) in human cells, leading to competition between siRNAs. In the case where the energy difference between the extremities of one of the siRNAs is largely superior to that of the other one, competition between the siRNAs appear to be favorable for the former. It is suggested that designing efficient siRNAs from thermodynamic characteristics is favored when siRNAs are incorporated into the RISC Loading Complex (RLC) rather than directly loaded into RISC.