HIV RNA packaging and lentivirus-based vectors

Since the mid-1990s, the number of publications on lentivirus-based vectors has expanded dramatically as people have realized the opportunity that they represent. High-titer helper-virus free transfer of genes to nondividing cells is a reality and it can only be a short time before clinical trials are initiated. The most efficient vector to date appears to be HIV-1 and it is no coincidence that this is the virus in which there is the greatest theoretical understanding of the encapsidation process and viral assembly. Basic studies in the other viruses are at an earlier stage and this is reflected to some extent in their relative inefficiency. Emphasis is placed in some publications on non-HIV-based vector systems having the additional safety feature of a viral vector not based on a human pathogen. As yet, this is largely a cosmetic advantage in that no system would be used which was capable of regenerating a full-length wild-type HIV and the vectors all have single round replication kinetics. More important will be elucidation of the mechanism of packaging in the different lentiviruses. Cis and trans packaging preferences may influence efficiency. Accurate delineation of packaging signals will be important. Most influential, however, will be a deeper understanding of all the viral and cellular factors involved in the packaging pathway.