Next-generation adenoviral vectors: New and improved

Abstract

The ability of Ad vectors efficiently to transduce genes into a variety of tissues fuels the wide interest in optimizing this vector for potential use in human gene therapy protocols. The natural biology of the Ad allows for a variety of modification schemes to be tested. Inevitably, comparisons between the vector classes described above will be made; these opinions should always be forwarded with caution, since the combination of multiple variables (inherent transgene immunogenicity, immune background of the host strain or species, antibody responses that may or may not be accompanied by CTL responses, doses of vector, promoter dysregulation, contamination with helper viruses, etc) may allow a modified vector to appear extremely useful in one set of experiments, and appear no different than an (E1-) Ad vector in another. In all likelihood, the modifications described will also be combined, either among themselves or with other vectoring systems (so called 'hybrid-vectors') to improve the biological performance profiles of gene transfer vectors in general. Therefore, the improvements already noted with the use of 'next-generation' Ad vectors may only be the beginning of a trend, especially when one contemplates the number of modifications that can now be theoretically introduced into future 'new and improved' Ad vectors.