1. ¹Program in Gene Therapy, Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA, USA
2. ²Virogenics Inc., San Diego, CA, USA

Correspondence: Professor PB McCray Jr, Program in Gene Therapy, Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA

Abstract

Replication defective vectors derived from simple retroviruses or the more complex genomes of lentiviruses continue to offer the advantages of long-term expression, cell and tissue specific tropism, and large packaging capacity for the delivery of therapeutic genes. The occurrence of adverse events caused by insertional mutagenesis in three patients in a gene therapy trial for X-linked SCID emphasizes the potential for problems in translating this approach to the clinic. Several genome-wide studies of retroviral integration are now providing novel insights into the integration site preferences of different vector classes. We review recent developments in vector design, integration, biosafety, and production.