Modern strategies for vaccination and gene therapy often involve the use of viral vectors. This is based on the fact that viruses have evolved useful techniques for invading the host and self-propagating. The goal is to harness those techniques to deliver immunizing antigens from a target disease organism or virus, while crippling the virus itself so that it cannot propagate and sicken its host. The simplest strategy has been the use of live, attenuated viruses, but this solution is obviously limited to vaccines for viral diseases. Even so, there is a concern that such attenuated viruses may mutate and become more virulent in the host. A more directed strategy is to design a vector based on a virus, but provide only the elements necessary for the virus to replicate within a cell, rather than propagate and spread throughout the host. Alphaviruses have been an attractive type of virus to use to design such a system. Flaviviruses, herpesviruses, lentiviruses and adenoviruses are other such systems.
All of these single- or restricted-cycle viruses utilize “helper” systems which separately provide some function of the parental virus from which they are derived. These helper systems are necessary to produce the single- or restricted-cycle virus particles, but ideally they are not carried along with those particles or recombined with the nucleic acids in the particles. However, whenever all portions of a viral genome are present in a cell at the same time, even if only transiently, there is the possibility that these elements will recombine to produce the parental virus.