Lentiviruses as Vectors for CNS Diseases

Abstract

During the past decade, mutations implicated in familial forms of CNS diseases have been identified (MARTIN 1995). The subsequent development of transgenic mouse models (AGUZZI et al. 1996), the use of gene-chip technology (SERAFINI 1999) and the development of functional imaging (PICCINI et al. 1999) have drastically modified our understanding of the molecular events leading to the cellular dysfunction and ultimately the degeneration of specific populations of neurons. These scientific advances offer an opportunity to explore gene therapy approaches for CNS diseases. The presence of the blood-brain barrier, the complex anatomical and functional organization of the brain and the post-mitotic and poor regenerative nature of the target cells, however, constitute important challenges for gene transfer approaches of neurological diseases. Viral vectors may address several of these issues (GLORIOSO et al. 2001). Whereas numerous viral vectors such as the adenoassociated virus (AAV), the helper-dependent adenovirus or even the herpes virus hold promise for CNS applications, lentiviral vectors are endowed with specific properties that make them very attractive for neurological diseases. They include the ability to infect and integrate into post-mitotic cells at high efficiency, the longterm expression of transgenes, the absence of sequences coding for viral proteins that may evoke an immune response and a cloning capacity of approximately 9kb which can accommodate most transgenes.