Targeting Sirna Missiles to Her2+ Breast Cancer
Annual rept. 15 May 2007-14 May 2008
CEDARS-SINAI MEDICAL CENTER LOS ANGELES CA
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The most significant findings here are that HerPBK10-siRNA complexes retain stability in whole serum and evade serum nuclease mediated degradation of the siRNA, thus providing an encouraging prediction that the complex will be stable in vivo. We also show that HerPBK10- siRNA complexes induce targeted cell death to HER2 but not HER2- cells in culture, suggesting that in vivo tumor targeting and cell death, as anticipated in the third year of this project, will be feasible. We show that the complex induces IFN-alpha secretion from HER2 but not HER2- cells, which likely contributes to the mechanism of targeted cell death by these complexes. Interestingly, we also found that the HerPBK10 protein alone also induced a similar pattern of IFN-alpha secretion, and will be examining the contribution of the carrier protein and siRNA toward the targeted cell death observed here. Finally, we show that the siRNA carrier, HerPBK10, undergoes tumor-preferential accumulation in tumor-bearing mice, and preferentially avoids of normal tissues and organs.
- Medicine and Medical Research