Chitosan (CS) has great potential as a nonvirus gene delivery vector, but its application is limited because of poor water solubility. Monomethyl poly(ethylene glycol) (mPEG)-graft-CS copolymers were synthesized by the reaction of mPEG-aldehyde (oxidized mPEG) with amino groups on CS chains; they showed enhanced solubility in water. Copolymers with various mPEG degrees of substitution (DS) and CS molecular weights were obtained, and their capabilities of DNA encapsulation were compared through gel retardation assay and particle size and potential measurements. The effects of different ratios of primary amines on CS to the phosphate groups on DNA (N/P ratios), DS, and molecular weights on particle size and encapsulation efficiency were investigated. The results show that high N/P ratios and proper DS were necessary for the formation of well-distributed complex particles. Among all of these samples, mPEG (3.55)-CS (50 kDa)/DNA complexes [where the parentheses following mPEG indicate DS (%), and the parentheses following CS indicate the molecular weight of CS] raised the zeta potential from negative to positive most quickly, yielded the smallest particle size, and were retarded in agarose gel at the lowest N/P ratio; this indicated the best efficiency of DNA encapsulation. On the contrary, mPEG (0.80)-CS (50 kDa)/DNA complexes raised the potential to positive most slowly, fluctuated around the value 0 from N/P ratios of 15 : 1 to 30 : 1, and were retarded in agarose gel at the highest N/P ratio; this indicated the lowest efficiency of encapsulating plasmids. Copolymers with desirable efficiencies of DNA encapsulation could be promising gene carriers. (C) 2008 Wiley Periodicals, Inc.