Peer-Reviewed Journal Details
Mandatory Fields
Monaghan, M,Greiser, U,Cao, H,Wang, W,Pandit, A
2012
October
Drug Delivery And Translational Research
An antibody fragment functionalized dendritic PEGylated poly(2-(dimethylamino) ethyl diacrylate) as a vehicle of exogenous microRNA
Published
WOS: 8 ()
Optional Fields
RNA interference Dendritic polymers Antibody conjugation Deactivation enhanced ATRP Gene therapy
2
406
414
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.
10.1007/s13346-012-0097-8
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