A recent report in Molecular Cell shows that retroviral vectors can be used to deliver DNA and protein in an efficient, dose-controlled, transient and targeted manner.

It had been proposed that pseudotransduction — transduction without proviral DNA integration into the host genome — could be used to express exogenous DNA. To explore this possibility, Christopher Baum and colleagues modified mouse leukaemia virus in two ways: they blocked proviral DNA integration by preventing reverse transcription of the viral RNA and inserted a nucleus-targeted site-specific recombinase Cre gene into the viral genome.

Using mouse and human fibroblasts that are engineered to express EGFP only on CRE-mediated recombination, the authors confirmed that these viral particles can deliver functional CRE in a dose-dependent and efficient manner — in some cases, up to 95% of the cell population were expressing EGFP following transfection. Importantly, pseudotransfection was cell-type specific — specificity for either mouse or human fibroblasts could be achieved by choosing appropriate envelope particles.

The authors were also interested in the mechanism that underlies pseudotransduction. A number of controls that lacked different viral components revealed that retroviral pseudotransduction requires retroviral particle formation and an active retroviral infection process triggered by Env — gag-pol, env and the retroviral packaging signal ψ are all required.

Because the reverse transcription step was not required for pseudotranscription, the authors suggest that this process could be extended to other viruses and propose a new term for it — particle-mediated mRNA transfer (PMT).

The ability to express Cre in a transient and targeted manner is useful in itself, but the authors have a more ambitious vision. They suggest that PMT could be particularly useful in cases where low and transient expression might lead to striking biological results, such as for the expression of receptors that are involved in the homing of circulating cells or transcription factors.