A Universal Protein Tag for Delivery of SiRNA-Aptamer Chimeras

Liu, Hong Yan; Gao, Xiaohu

final large complexes (typically 100 s nanometers) and the chemical composition of the nanocarriers can drastically change chimera's targeting profile, in vivo biodistribution, and clearance 23 . Furthermore, it is ideal to make the aptamer loop structure exposed and the siRNA block hidden for specific binding, but electrostatic condensation with cationic nanocarriers does not warrant that selectivity. As demonstrated previously, immobilizing siRNA-aptamer chimeras onto cationic nanoparticles via the siRNA end offers significantly improved silencing effect compared to condensing chimeras onto cationic nanoparticles through random sites 24 . This is understandable since (1) exposure of the siRNA end would only increase the chances of non-specific binding and reduce the stability siRNA against enzymatic degradation; and (2) interaction between cationic nanocarriers with anionic aptamers could alter aptamers' conformation and targeting capability 25 . Therefore, it is of critical importance to design a delivery system that is simple for potential regulatory approval and mass production, universal for all siRNAaptamer chimera, neutral and siRNA-binding specific to ensure aptamer targeting, and small to avoid major alteration of chimera's biodistribution profile. A system simultaneously achieving these features could expedite clinically translation of the highly promising siRNA-aptamer chimera technology.