Quaternized celluloses (QCs) with different molecular weight (M(w)) and degree of cationic substitution (DS) were homogeneously synthesized in NaOH/urea aqueous solutions and were studied as gene carriers. QCs were evaluated for efficacy of nanoparticle formation, DNA binding efficiency, morphology, and in vitro gene transfection efficiency. The factors affecting the transfection efficiency, e.g., M(w), DS, and N/P ratios, have been evaluated. The cytotoxicity of QCs and QC/DNA complexes were evaluated in 293T cells and were found to be relatively low compared with 25 kDa PEI and PEI/DNA complex, which increased slightly with increasing of M(w) and DS. All QCs obtained could bind DNA efficiently, and QC/DNA complexes exhibited effective transfection in comparison to the naked DNA. More importantly, the QC/DNA complexes, were stable and the transfection efficiency was not inhibited in the presence of serum. The results revealed an important combined effect between M(w) and DS of QCs in determining transgene expression, and QCs with M(w) of about 8 x 10(4) g/mol and DS of about 0.6 displayed relatively higher transfection efficiencies attributed to the intermediate stability.