Lentiviral Vectors: Not Just For Gene Therapy

Lentiviral vectors (LVs) are viral-based gene delivery systems that can stably deliver genes or RNAi into primary cells or cell lines with up to 100% efficiency. LVs bind to target cells using an envelope protein which allows for release of the LV RNA containing the gene or gene silencing sequence into the cell. The LV’s RNA is then converted into DNA using an enzyme called reverse transcriptase by a process called reverse transcription. The DNA pre-integration complex then enters the nucleus and integrates into the target cell’s chromosomal DNA. Lentiviral vectors are the only genetic vector system that affords both high and stable gene delivery. Other vectors, such as adeno-associated viral vectors can persist in nondividing tissues, but are cured from cells once they divide. Lentiviral vectors integrate their payload sequence into the chromosome of transduced cells so that it is copied along with the chromosomal DNA when the cell divides. The properties of lentiviral vectors make them highly suitable for efficient and stable gene delivery into cell lines and primary cells. One of the discriminating features of LVs is their ability to integrate into non-dividing cells; this is in contrast to other vectors that either don’t integrate efficiently into chromosomal DNA (for example, nonviral, adenoviral and adenoviral-associated vectors), or can only integrate upon cell division (for example, conventional retroviral vectors). (The structure and mode of action of a lentiviral vector is shown in Figure 1.) Most researchers still view lentiviral vectors as a gene therapy instrument – given their demonstrated safety and encouraging results in past and ongoing clinical trials – but in fact they have potential in many different applications. This article will provide additional detail on certain of these applications, including virus-like particle (VLP) creation, protein production and use as a research tool.