Gene transfer systems derived from Visna virus: analysis of virus production and infectivity

Efficient transfer of therapeutic genes into nondividing human cells can be accomplished by inserting the genes into lentiviruses and infecting the cells with the modified viruses. The most developed lentivirus gene transfer systems are based on HIV-1, but because of the widespread HIV epidemic, the use of HIV-based vectors for gene therapy may be associated with a safety risk. In an attempt to find another lentivirus which can transduce human cells and might be safer than HIV-1, we generated gene transfer constructs based on the sheep lentivirus Visna. Molecular analysis of the constructs in a transient production system indicated that Visna produced as many mature virus particles as did HIV-1. Moreover, the virus particles incorporated a heterologous surface protein marker-gene-containing vector RNAs as efficiently as did HIV-1. However, the Visna virus transduced target cells poorly because of defects in reverse transcription and integration of the vector. Further modifications must be made to the Visna gene transfer system if the system is to be used in clinical gene therapy applications.