Retroviral-mediated gene therapy--safety considerations and preclinical studies

Retroviral mediated gene transfer (1) is now a clinical reality, with several protocols being conducted. The features that have made these vectors appropriate for the first clinical studies in humans are (i) they are derived from well characterized murine retroviruses (ii) many foreign genes have been expressed in many different cell types, and transduction efficiency can be very high (iii) helper or wild type virus free vectors can be obtained in good titer and (iv) the number of sites of proviral integration is limited although the site of integration in the genome is random. Most of the work described has been conducted in the laboratories of our collaborators, notably Drs. W. French Anderson, R. Michael Blaese, Steven A. Rosenberg, and Arthur W. Nienhuis at the National Institutes of Health, Bethesda, MD, and Dr. Malcolm K. Brenner at St. Jude's Hospital in Memphis, as well as work conducted at Genetic Therapy, Inc. But it is very important to appreciate that retroviral vectors themselves were developed from the pioneering work of researchers in a large number of laboratories in the early and mid 80's.