Among many obstacles in achieving desired efficacy of nonviral gene delivery, endosomal escape and dissociation of therapeutic genes from carriers have been considered as the most crucial steps. Degradable nanoparticles were synthesized by polymerizing cationic degradable monomers in the presence of plasmid DNA encoding GFP and luciferase as biomarkers of successful transfection. The employed method enabled us to obtain controllable size, configuration, and degradability of nanoparticles as well as further conjugation with other modalities such as molecular targeting agents and imaging probes. The degradability of nanoparticles facilitated endosomal/lysosomal escape of DNA by destabilizing the compartments in ways independent of proton-sponge effect. Moreover, plasmid DNA was efficiently freed from the nanoparticle and efficiently expressed. The characterizations of the nanoparticles including size, morphology, and condensation efficiency will be presented along with pH-sensitive release of encapsulated plasmid from the nanopaticles. Enhanced efficiency of ex vivo gene delivery confirmed by transfecting murine fibroblast, and effects of properties of nanoparticles including size, surface charge, degradability, and PEGylation will also be shown. A possibility of using the highly versatile degradable nanoparticle carriers for gene therapy will be conveyed with the PEG stabilized particles which gave expression levels higher than poly-L-lysine particles for up to 7 days post administration by transtracheal instillation as assessed by bioluminescence from airway epithelial cells of an animal model.