Recent Developments in Retroviral-Mediated Gene Transduction

Retroviral vectors are powerful tools for gene transfer for experimentation as well as for clinical applications. These vectors are devoid of viral genes, are nonimmunogenic, and insert the therapeutic gene in the host chromosome ensuring its transmission to daughter cells. However, despite the use of retroviral gene transfer in many gene therapy trials to date, significant limitations remain. An important concern that must be fully addressed before retroviral gene delivery can pass the trial stage is the potential generation of replication-competent virus (RCV) by recombination during packaging. Other potential limitations include insertional mutagenesis in the target cell, inactivation of viral particles by the human complement system, limited ability to target both particular cell types and specific regions of the target cell chromosome, and the phenomenon of transgene silencing. Encouragingly, advances are being made rapidly on all these fronts, advances which take into account a considerable body of previous knowledge gathered with murine retroviruses and a growing, more complete understanding of lentivirus molecular biology. As a large body of literature on the construction and assessment of retroviral vector modifications already exists (1–3), we have attempted to summarize in this review a series of the recent major improvements in retroviral vector development in the context of the problems that they are attempting to address.