Collapsing retroviruses for efficient delivery of viro-toxic cargoes
Mullally, C.; Stefanovska, B.; Chen, Y.; Gupta, H.; Carpenter, M.; Harris, R.
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Retroviruses are excellent tools for delivering and expressing transgenic cargoes with broad utility in research and therapy. However, many cargoes including virus restriction factors can dramatically limit virus production and/or infectivity. An extreme viro-toxic cargo is the DNA cytosine deaminase APOBEC3B, which potently restricts retrovirus infectivity by a direct cDNA deamination-dependent mechanism. To overcome viro-toxicity, an APOBEC3B minigene cargo is disrupted by a translation stop cassette flanked by a direct repeat of its own sequence. The integrity of the minigene is reconstituted naturally by retroviral recombination during transduction. Efficiency can be improved from 90% to nearly 100% by coupling the minigene to the translation of a downstream selectable marker. Collapsing retrovirus (CRV) technology enables the functional delivery of APOBEC3B to a target cell population and may have broad utility for delivering viro-toxic cargoes.
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