Active Nuclear Import of Mammalian Cell-Expressible DNA Origami.

Autor: Liedl A; Department of Biosciences, School of Natural Sciences, Technical University of Munich, Am Coulombwall 4a, 85748 Garching, Germany.; Munich Institute of Biomedical Engineering, Technical University of Munich, Boltzmannstraße 11, 85748 Garching, Germany., Grießing J; Department of Biosciences, School of Natural Sciences, Technical University of Munich, Am Coulombwall 4a, 85748 Garching, Germany.; Munich Institute of Biomedical Engineering, Technical University of Munich, Boltzmannstraße 11, 85748 Garching, Germany., Kretzmann JA; Department of Biosciences, School of Natural Sciences, Technical University of Munich, Am Coulombwall 4a, 85748 Garching, Germany.; Munich Institute of Biomedical Engineering, Technical University of Munich, Boltzmannstraße 11, 85748 Garching, Germany., Dietz H; Department of Biosciences, School of Natural Sciences, Technical University of Munich, Am Coulombwall 4a, 85748 Garching, Germany.; Munich Institute of Biomedical Engineering, Technical University of Munich, Boltzmannstraße 11, 85748 Garching, Germany.
Jazyk: angličtina
Zdroj: Journal of the American Chemical Society [J Am Chem Soc] 2023 Mar 08; Vol. 145 (9), pp. 4946-4950. Date of Electronic Publication: 2023 Feb 24.
DOI: 10.1021/jacs.2c12733
Abstrakt: DNA origami enables the creation of complex 3D shapes from genetic material. Future uses could include the delivery of genetic instructions to cells, but nuclear import remains a major barrier to gene delivery due to the impermeability of the nuclear membrane. Here we realize active nuclear import of DNA origami objects in dividing and chemically arrested mammalian cells. We developed a custom DNA origami single-strand scaffold featuring a mammalian-cell expressible reporter gene (mCherry) and multiple Simian virus 40 (SV40) derived DNA nuclear targeting sequences (DTS). Inclusion of the DTS within DNA origami rescued gene expression in arrested cells, indicating that active transport into the nucleus occurs. Our work successfully adapts mechanisms known from viruses to promote the cellular expression of genetic instructions encoded within DNA origami objects.
Databáze: MEDLINE
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