An investigation of encapsulated plasmid DNA release from degradable poly(ethylene glycol)-co-poly(glycolic acid) hydrogels (PEG-co-PGA) is presented. We determined by varying the chemistry of the cross-linker group, significant variations in hydrogel degradation kinetics could be achieved to control the release profiles of plasmid DNA. We prepared three analogues of PEG-co-PGA hydrogels by a photopolymerization process and measured variation in degradation rates by monitoring mechanical properties and release of plasmid DNA. 1H 1D DOSY NMR (one-dimensional diffusion ordered nuclear magnetic resonance spectroscopy) was used to measure conversion of vinyl groups after photocross-linking. Nearly full vinyl conversion was reached after 10 min exposure under ultraviolet light. Gel electrophoresis analysis confirmed that plasmid DNA remained structurally intact after photoencapsulation and release from the gels. This approach provides an additional strategy for controlling the release of biologically active compounds from hydrogels.