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Henn, Dominic; Zhao, Dehua; Sivaraj, Dharshan; Trotsyuk, Artem; Bonham, Clark Andrew; Fischer, Katharina S.; Kehl, Tim; Fehlmann, Tobias; Greco, Autumn H.; Kussie, Hudson C.; Moortgat Illouz, Sylvia E.; Padmanabhan, Jagannath; Barrera, Janos A.; Kneser, Ulrich; Lenhof, Hans-Peter; Januszyk, Michael; Levi, Benjamin; Keller, Andreas; Longaker, Michael T.; Chen, Kellen; Qi, Lei S.; Gurtner, Geoffrey C.

Cas9-mediated knockout of Ndrg2 enhances the regenerative potential of dendritic cells for wound healing

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  • Medientyp: E-Artikel
  • Titel: Cas9-mediated knockout of Ndrg2 enhances the regenerative potential of dendritic cells for wound healing
  • Beteiligte: Henn, Dominic; Zhao, Dehua; Sivaraj, Dharshan; Trotsyuk, Artem; Bonham, Clark Andrew; Fischer, Katharina S.; Kehl, Tim; Fehlmann, Tobias; Greco, Autumn H.; Kussie, Hudson C.; Moortgat Illouz, Sylvia E.; Padmanabhan, Jagannath; Barrera, Janos A.; Kneser, Ulrich; Lenhof, Hans-Peter; Januszyk, Michael; Levi, Benjamin; Keller, Andreas; Longaker, Michael T.; Chen, Kellen; Qi, Lei S.; Gurtner, Geoffrey C.
  • Erschienen: Springer Science and Business Media LLC, 2023
  • Erschienen in: Nature Communications
  • Sprache: Englisch
  • DOI: 10.1038/s41467-023-40519-z
  • ISSN: 2041-1723
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>Chronic wounds impose a significant healthcare burden to a broad patient population. Cell-based therapies, while having shown benefits for the treatment of chronic wounds, have not yet achieved widespread adoption into clinical practice. We developed a CRISPR/Cas9 approach to precisely edit murine dendritic cells to enhance their therapeutic potential for healing chronic wounds. Using single-cell RNA sequencing of tolerogenic dendritic cells, we identified N-myc downregulated gene 2 (<jats:italic>Ndrg2</jats:italic>), which marks a specific population of dendritic cell progenitors, as a promising target for CRISPR knockout. <jats:italic>Ndrg2</jats:italic>-knockout alters the transcriptomic profile of dendritic cells and preserves an immature cell state with a strong pro-angiogenic and regenerative capacity. We then incorporated our CRISPR-based cell engineering within a therapeutic hydrogel for in vivo cell delivery and developed an effective translational approach for dendritic cell-based immunotherapy that accelerated healing of full-thickness wounds in both non-diabetic and diabetic mouse models. These findings could open the door to future clinical trials using safe gene editing in dendritic cells for treating various types of chronic wounds.</jats:p>
  • Zugangsstatus: Freier Zugang