Investigation of the pathogenesis of rheumatoid arthritis has led us to discover new candidate molecules as targets in RA therapeutic strategies. Gene therapy offers one of the best tools to deliver of such therapeutic molecules into the affected joints. In the past, many gene therapy trials preferred viral delivery methods to non-viral methods because of the difference in gene transfer efficiency. However, viral methods have many unresolved problems mainly related to safety. One example is immunogenicity of adenovirus vector. Efforts have been made to improve viral vectors for clinical application.