Gene therapy is the treatment of disease by transferring genetic material into specific cells of the patient. It has been heavily investigated for the treatment of many diseases, including cancer. However, since unprotected gene will be easily degraded by endogenous nucleases, the success of gene therapy is largely dependent on the development of gene vectors that can efficiently deliver genes to target cells with minimal toxicity. Cationic polymers are promising candidates because of their facile synthesis, high stability and flexibility in functionalization, but most of them suffer due to low efficiency or high toxicity. Based on the previous research on polymeric gene carriers in the Saltzman Lab, I have synthesized a series of poly (amine-co-esters) containing ortho ester groups and these materials showed significantly higher gene delivery efficiency and greatly lower toxicity than the commercial gene vectors.