The objectives of the current study were to design and characterize poly(ethylene glycol) (PEG)-based carriers for antisense oligonucleotide (AON) delivery that would gradually release the AON upon the enzymatic degradation of a complementary nuclease-sensitive sequence (SON). A phosphodiester SON was conjugated to one extremity or to the central part of PEG (molecular weight 10 or 20 K). The PEG-SON was hybridized to a nuclease-resistant phosphorothioate AON analog. Compared to the non-PEGylated duplex, the PEG-SON/AON derivative had a modest impact on the degradation kinetics of SON as monitored by a fluorescence dequenching assay performed in the presence of DNase 1. The reaction rate depended on the grafting position of SON and on the PEG’s molecular weight. To further control the release rate, PEG-SON/AON conjugates were complexed to poly(amidoamine) (PAMAM) dendrimers of different generations (G). Interaction with PAMAMs of G3 and G5 yielded monodisperse polyion complex micelles (PICMs) with average mean sizes ranging from 70 to 100 nm. The PICMs were found to decrease the catalytic reaction rate by 20 to 100 fold; the slowest release kinetics being achieved with PEG10K-SON/AON/G5 PAMAM. The PEGylated conjugates reported in this manuscript as well as their self-assemblies with PAMAMs, could prove potentially useful to confer prolonged circulating properties to nucleic acid drugs and release them in a sustained manner.