An antibody fragment functionalized dendritic PEGylated poly(2-(dimethylamino)ethyl diacrylate) as a vehicle of exogenous microRNA

Drug Delivery and Translational Research
M MonaghanAbhay Pandit

Abstract

The translation of interfering RNA to the clinic requires more effective delivery agents to enable safe and efficient delivery. The aim of this work was to create a multi-functional delivery agent using deactivation enhanced ATRP synthesis of poly(dimethylamino)ethyl methacrylate (pDMAEMA)-co-PEGMEA/PEGDA (pD-b-P/DA) with linear pDMAEMA as a macro-initiator. The pD-b-P/DA was characterized for its potential to bind synthetic microRNA mimics to form structures and reacted with antibody-derived fragments (Fabs) using Michael-type addition. Conjugation of antibody fragments was verified using SDS-PAGE. Functional delivery of these interfering RNA complexes was proven using a dual luciferase reporter assay. Functional silencing of a reporter gene was improved by complexation of microRNA mimics with pD-b-P/DA alone and with Fab-decorated pD-b-P/DA. The improved silencing with Fab-decorated pD-b-P/DA was evident at 48 h but disappeared at 96 h. The resultant agent enables complexation of nucleic acid (microRNA mimic) and facile conjugation of antibody fragments via a Michael-type addition. In conclusion, this platform is effective at silencing in this reporter system and has potential as an effective delivery system of interfering RNA.

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Citations

Feb 10, 2016·Scientific Reports·Kyung-Ho LeeDong-Myung Kim
Jul 9, 2013·Drug Discovery Today·Ahmed AiedWenxin Wang
Dec 29, 2015·Biochemical and Biophysical Research Communications·Leonid BreydoWenxin Wang
Jan 17, 2015·Iranian Red Crescent Medical Journal·Saeid SafariSeyed Moayed Alavian

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