The Williamsburg BioProcessing Foundation Reference Materials for Retroviruses and Lentiviruses June 5, 2002: The Sheraton Hotel - Boston, MA, USA Final Report

A growing number of retrovirus -based vectors for gene therapy applications are being developed. Vectors based on animal gammaretroviruses ( formerly oncoretroviruses) such as the amphotropic strain of murine leukemia virus (MuLV) have been in use for ex vivo transductions of hematolymphoid cells for over a decade. Most vectors actually used for clinical gene transfer are hybrids of amphotropic (A) and Moloney (Mo) strains of MuLV – the core proteins, Gag and Pol, are derived from MoMuLV, while the envelope protein, Env, is derived from A -MuLV. While these vectors have demonstrated proof of principle in transfer and expression of transgenes, they have had only limited success in clinical settings. The lack of success has been related to the inability of these vectors to transduce non -dividing cells. Non-dividing cells often represent a large proportion of target cells. In addition, their use for in vivo gene therapy applications has been limited due to complement inactivation and poor structural stability. To overcome these limitations, researchers have focused attention on lentiviruses for the development of replication -deficient lentivectors since lentiviruses are potentially capable of transducing both dividing and non -dividing cells and appear to be somewhat more robust for in vivo applications. However, several groups have chos en pathogenic human lentiviruses, human immunodeficiency virus-1 (HIV-1) and -2 (HIV-2), or non-human primate lentiviruses, such as simian immunodeficiency virus, as the bases for lentivector development, leading to growing concerns about the relative safe ty of such vectors. Lentivectors based on non -primate lentiviruses, e.g. feline immunodeficiency virus (FIV), equine infectious anemia virus (EIAV), are also being developed which appear to pose less of a safety risk, but less is known generally about thes e viruses than HIV -1 and there could be unpredictable risks with their clinical use. (General issues about lentivirus vectors were previously discussed by a US FDA advisory committee in October 2001; visit http://www.fda.gov/ohrms/dockets/ac/cber01.htm#Biological%20Response for details).