The controversial role of adenoviral-derived vectors in gene therapy programs: where do we stand?

The high immunogenicity of recombinant adenoviral vectors is one of the major issues in the field of gene therapy. Adenoviral-based vectors are susceptible both to cytotoxic T-lymphocyte and humoral immune responses. In addition, leaky adenoviral genes also render transduced cells susceptible to host immune responses. These are the main reasons why adenoviral-based vectors are not suitable to correct genetic disorders, which require long-term expression of the transgene. Another limit to long-term transgene expression is posed by the fact that adenoviral-based vectors do not integrate their genome into the cellular chromosomal DNA of transduced cell populations. As it stands, adenoviral-mediated gene transfer is a promising tool for cancer therapy and for genetic immunization programs against infectious diseases, provided that host immune responses are carefully controlled.