A Universal Protein Tag for Delivery of SiRNA-Aptamer Chimeras

Liu, Hong Yan; Gao, Xiaohu

Design, synthesis, and characterization of siRNA-aptamer chimera. To evaluate the universal protein tag for siRNA-aptamer chimera, we first designed and made a chimera based on the protocols described by Dassie and coworkers, taking advantage of the shortened aptamer sequence for specific targeting of PSMA as well as the optimized siRNA strands with enhanced therapeutic potency 15 . The PSMA targeting aptamer was kept in our chimera, because PSMA has been identified as one of the most attractive cell surface markers for both prostate epithelial cells and neovascular endothelial cells 36 . Accumulation and retention of PSMA targeting probes at the site of tumor growth is the basis of radioimmunoscintigraphic scanning (e.g., ProstaScint scan) and targeted therapy for human prostate cancer metastasis. We replaced their siRNA sequence with a siRNA silencing GFP expression, because GFP is the best model for quantitative assessment of the silencing effect using optical imaging and flow cytometry.