Vaccinia viral/retroviral chimeric vectors

Retroviral vectors have become important tools in gene therapy due to a number of desirable properties, including efficient gene delivery and stable genomic integration. Some shortcomings, however, still remain to be solved. Retroviral vectors cannot be grown to as high titers as for example adenoviruses or vaccinia viruses, they tend to be unstable and are sensitive to lysis by complement when transfused into patients. The search for more robust retroviral delivery systems has led to the development of hybrid viral vectors trying to combine the broadly estimated features of retroviral vectors with advantageous properties of a second viral vector system. Chimeric systems with retroviruses and adeno-alphavirus and herpesviruses have been reported. This review is dedicated to vaccinia virus, a widely used vector in molecular and cell biology, as a chimeric carrier for retroviral vector units. In the first poxviral/retroviral constructs, retroviral vector units integrated into a defective vaccinia vector, gave rise to transduction competent particles. Due to the high insertion capacity of the vaccinia system, also the packaging components could be inserted into the carrier virus resulting in a system that is independent of retroviral packaging cell lines. Moreover, since vaccinia is a cytoplasmic virus that does not recognize nuclear transcription and processing signals, retroviral vectors with introns and internal transcription stops could be constructed that transduce complex gene cassettes. The topic of this review is the vaccinia viral / retroviral vector system and possible applications to gene therapy.