Trends in Biotechnology
Harnessing HIV for therapy, basic research and biotechnology
Section snippets
The basics of lentivector-mediated gene delivery
Like their gammaretrovirus-based predecessors, such as those based on murine leukemia virus (MLV), lentiviral vectors integrate their cargo into the chromosomes of target cells without transferring virus-derived coding sequences. Unlike MLV vectors, however, lentivectors can mediate this process in nondividing cells, which is a great asset for many experimental and clinical situations. A detailed description of currently available lentivector designs is beyond the scope of this review and can
The most promising therapeutic targets of lentivectors
Lentivectors can govern the efficient delivery, integration and long-term expression of transgenes into nondividing cells both in vitro and in vivo. As such, they represent attractive tools for most potential targets of gene therapy, whether the targets are early precursors or terminally differentiated cells (Box 1). So far, however, this expectation has been essentially fulfilled only in the CNS, the hematopoietic system and, to a lesser extent, in the liver, and more work is necessary to
Vector targeting
Minimizing host immune responses and avoiding the potentially toxic, off-target effects of transgene expression are important concerns. Vector targeting via modification of the virion envelope is in its infancy; however, restriction can be achieved at the transcriptional level by incorporating tissue-specific promoters and enhancers into lentivectors. This feature is particularly important when vectors are used to transduce tissues or organs by in vivo administration. In this delivery route,
Future perspectives
In less than a decade, lentivectors have become gene-delivery vehicles that are most actively exploited in many areas of basic and applied research. In gene therapy, numerous studies have confirmed that lentivectors can effect robust and highly efficient gene transfer into organs and tissues that are out of reach for many other gene-delivery systems. Although there is no ‘ideal’ vector that can function in all applications, the relatively large capacity of lentivectors and their integration
Acknowledgements
Research in our laboratory is supported by the Swiss National Science Foundation, the European Union and the Institut Clayton de la Recherche M.W. thanks Jola Szulc for helpful discussions and critical reading of the manuscript. We apologize to those whose work could not be cited owing to space considerations.
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