Piggybacking functionalized DNA nanostructures into live-cell nuclei.

Autor: Roozbahani GM; Department of Physics, The Ohio State University, Columbus, OH 43210, USA.; Department of Mechanical and Aerospace Engineering, The Ohio State University, Columbus, OH 43210, USA., Colosi PL; Department of Physiology, University of Pennsylvania, Philadelphia, PA 19104, USA., Oravecz A; Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch 67404, France.; Centre National de la Recherche Scientifique, UMR7104, Illkirch 67404, France.; Institut National de la Santé et de la Recherche Médicale, U1258, Illkirch 67404, France.; Université de Strasbourg, Illkirch 67404, France., Sorokina EM; Department of Physiology, University of Pennsylvania, Philadelphia, PA 19104, USA., Pfeifer W; Department of Physics, The Ohio State University, Columbus, OH 43210, USA.; Department of Mechanical and Aerospace Engineering, The Ohio State University, Columbus, OH 43210, USA., Shokri S; Department of Physics, The Ohio State University, Columbus, OH 43210, USA., Wei Y; Biophysics Graduate Program, The Ohio State University, Columbus, OH 43210, USA., Didier P; Université de Strasbourg, Illkirch 67404, France.; Laboratoire de Biophotonique et Pharmacologie, Illkirch 67401, France., DeLuca M; Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC 27708, USA., Arya G; Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC 27708, USA., Tora L; Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch 67404, France.; Centre National de la Recherche Scientifique, UMR7104, Illkirch 67404, France.; Institut National de la Santé et de la Recherche Médicale, U1258, Illkirch 67404, France.; Université de Strasbourg, Illkirch 67404, France., Lakadamyali M; Department of Physiology, University of Pennsylvania, Philadelphia, PA 19104, USA.; Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.; Epigenetics Institute, University of Pennsylvania, Philadelphia, PA 19104, USA., Poirier MG; Department of Physics, The Ohio State University, Columbus, OH 43210, USA.; Biophysics Graduate Program, The Ohio State University, Columbus, OH 43210, USA.; Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA., Castro CE; Department of Mechanical and Aerospace Engineering, The Ohio State University, Columbus, OH 43210, USA.; Biophysics Graduate Program, The Ohio State University, Columbus, OH 43210, USA.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2024 Jul 05; Vol. 10 (27), pp. eadn9423. Date of Electronic Publication: 2024 Jul 05.
DOI: 10.1126/sciadv.adn9423
Abstrakt: DNA origami nanostructures (DOs) are promising tools for applications including drug delivery, biosensing, detecting biomolecules, and probing chromatin substructures. Targeting these nanodevices to mammalian cell nuclei could provide impactful approaches for probing, visualizing, and controlling biomolecular processes within live cells. We present an approach to deliver DOs into live-cell nuclei. We show that these DOs do not undergo detectable structural degradation in cell culture media or cell extracts for 24 hours. To deliver DOs into the nuclei of human U2OS cells, we conjugated 30-nanometer DO nanorods with an antibody raised against a nuclear factor, specifically the largest subunit of RNA polymerase II (Pol II). We find that DOs remain structurally intact in cells for 24 hours, including inside the nucleus. We demonstrate that electroporated anti-Pol II antibody-conjugated DOs are piggybacked into nuclei and exhibit subdiffusive motion inside the nucleus. Our results establish interfacing DOs with a nuclear factor as an effective method to deliver nanodevices into live-cell nuclei.
Databáze: MEDLINE