title: An antibody fragment functionalized dendritic PEGylated poly(2-(dimethylamino)ethyl diacrylate) as a vehicle of exogenous microRNA.
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.
authors: Network of Excellence for Functional Biomaterials, National University of Ireland, Galway, Ireland.
authors: M
authors: M
authors: Monaghan
authors: U
authors: U
authors: Greiser
authors: H
authors: H
authors: Cao
authors: W
authors: W
authors: Wang
authors: A
authors: A
authors: Pandit