Conditional Mutagenesis: An Approach to Disease Models

Osten P, Grinevich V, Cetin A, P. Osten, V. Grinevich, A. Cetin, Osten, P., Grinevich, V., Cetin, A.

Viruses are intracellular parasites with simple DNA or RNA genomes. Virus life revolves around three steps: infection of a host cell, replication of its genome within the host cell environment, and formation of new virions; this process is often but not always associated with pathogenic effects against the host organism. Since the mid-1980s, the main goal of viral vectorology has been to develop recombinant viral vectors for long-term gene delivery to mammalian cells, with minimal associated toxicity. Today, several viral vector systems are close to achieving this aim, providing stable transgenic expression in many different cell types and tissues. Here we review application characteristics of four vector systems, derived from adeno-associated viruses, adenoviruses, retroviruses and herpes simplex virus-1, for in vivo gene delivery. We discuss the transfer capacity of the expression vectors, the stability of their transgenic expression, the tropism of the recombinant viruses, the likelihood of induction of immunotoxicity, and the ease (or difficulty) of the virus production. In the end, we discuss applications of these vectors for delivery of three molecular systems for conditional mutagenesis, two for inducible transcriptional control of transgenic expression (the tet and the dimerizer systems), and the third one for inducible control of endogenous gene expression based on RNA interference.