Efficient transient genetic manipulation in vitro and in vivo by prototype foamy virus-mediated nonviral RNA transfer

Martin V Hamann, Nicole Stanke, Erik Müllers, Kristin Stirnnagel, Sylvia Hütter, Benedetta Artegiani, Sara Bragado Alonso, Federico Calegari, Dirk Lindemann

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Samenvatting

Vector systems based on different retroviruses are widely used to achieve stable integration and expression of transgenes. More recently, transient genetic manipulation systems were developed that are based on integration- or reverse transcription-deficient retroviruses. Lack of viral genome integration is desirable not only for reducing tumorigenic potential but also for applications requiring transient transgene expression such as reprogramming or genome editing. However, all existing transient retroviral vector systems rely on virus-encoded encapsidation sequences for the transfer of heterologous genetic material. We discovered that the transient transgene expression observed in target cells transduced by reverse transcriptase-deficient foamy virus (FV) vectors is the consequence of subgenomic RNA encapsidation into FV particles. Based on this initial observation, we describe here the establishment of FV vectors that enable the efficient transient expression of various transgenes by packaging, transfer, and de novo translation of nonviral RNAs both in vitro and in vivo. Transient transgene expression levels were comparable to integrase-deficient vectors but, unlike the latter, declined to background levels within a few days. Our results show that this new FV vector system provides a useful, novel tool for efficient transient genetic manipulation of target tissues by transfer of nonviral RNAs.

Originele taal-2Engels
Pagina's (van-tot)1460-1471
Aantal pagina's12
TijdschriftMolecular therapy : the journal of the American Society of Gene Therapy
Volume22
Nummer van het tijdschrift8
DOI's
StatusGepubliceerd - aug. 2014
Extern gepubliceerdJa

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