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. 2001 Dec;19(12):1155-61.
doi: 10.1038/nbt1201-1155.

Selective enhancement of gene transfer by steroid-mediated gene delivery

A Rebuffat  1 , A Bernasconi, M Ceppi, H Wehrli, S B Verca, M Ibrahim, B M Frey, F J Frey, S Rusconi
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Selective enhancement of gene transfer by steroid-mediated gene delivery

A Rebuffat et al. Nat Biotechnol. 2001 Dec.

Abstract

The incorporation of transgenes into the host cells' nuclei is problematic using conventional nonviral gene delivery technologies. Here we describe a strategy called steroid-mediated gene delivery (SMGD), which uses steroid receptors as shuttles to facilitate the uptake of transfected DNA into the nucleus. We use glucocorticoid receptors (GRs) as a model system with which to test the principle of SMGD. To this end, we synthesized and tested several bifunctional steroid derivatives, finally focusing on a compound named DR9NP, consisting of a dexamethasone backbone linked to a psoralen moiety using a nine-atom chemical spacer. DR9NP binds to the GR in either its free or DNA-crosslinked form, inducing the translocation of the GR to the nucleus. The expression of transfected DR9NP-decorated reporter plasmids is enhanced in dividing cells: expression of steroid-decorated reporter plasmids depends on the presence of the GR, is independent of the transactivation potential of the GR, and correlates with enhanced nuclear accumulation of the transgene in GR-positive cells. The SMGD effect is also observed in cells naturally expressing GRs and is significantly increased in nondividing cell cultures. We propose that SMGD could be used as a platform for selective targeting of transgenes in nonviral somatic gene transfer.

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Comment in

  • Nuclear security breached.
    Wolff JA, Sebestyén MG. Wolff JA, et al. Nat Biotechnol. 2001 Dec;19(12):1118-20. doi: 10.1038/nbt1201-1118. Nat Biotechnol. 2001. PMID: 11731776 No abstract available.

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