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.
Keywords: Mouse Leukemia Virus, Human Immunodeficiency Virus, retroviral imaging, retroviral vector, retroviral protein
transfer, virus-like particle, by-products, DNA
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