Retroviral Protein Transfer: Falling Apart to Make an Impact

Retroviral vectors represent evolutionarily optimized gene delivery vehicles, which stably integrate their coding DNA into the host cell genome. In contrast to other gene delivery platforms, retroviral entry and integration are relatively efficient due to the utilization of cellular mechanisms for particle transport, DNA repair and gene expression, features that can be exploited for gene therapy and cell modification. Arresting the retroviral life cycle at specific steps, i.e. prior to reverse transcription or integration, allows for the utilization of intermediate structures (mRNA) or by-products (episomes) as tools for transient applications. However, it is often overlooked that retroviral particles are composed of up to 2500 Gag structural proteins, as well as further proteins involved in viral replication, all of which can be harnessed for the transfer of heterologous proteins into target cells. In this review, we describe the general biology of retroviruses and their derived vector systems, and then discuss the potential of engineering their protein components. We focus on lentiviral, gammaretroviral and alpharetroviral vector systems, and address current developments in the visualization of retrovirus-cell interactions (live cell imaging), and potential applications of engineered retroviral particles in biotechnology and biomedical research. Compared to conventional protein transduction techniques, we envisage protein-transducing retrovirus-like particles as a highly flexible platform for the efficient and cell-targeted delivery of designer proteins, even in combination with transduction of retroviral mRNA, episomal DNA or integrating DNA.