DNA origami scaffold promoting nerve guidance and regeneration

Jonathan Giron, Merav Antman-Passig, Neta Zilony, Hadas Schori, Ido Bachelet, Orit Shefi

Research output: Contribution to journalArticlepeer-review

Abstract

Self-assembly of biological elements into biomimetic cargo carriers for targeting and delivery is a promising approach. However, it still holds practical challenges. We developed a functionalization approach of DNA origami (DO) nanostructures with neuronal growth factor (NGF) for manipulating neuronal systems. NGF bioactivity and its interactions with the neuronal system were demonstrated in vitro and in vivo models. The DO elements fabricated by molecular self-assembly have manipulated the surrounding environment through static spatially and temporally controlled presentation of ligands to the cell surface receptors. Our data showed effective bioactivity in differentiating PC12 cells in vitro. Furthermore, the DNA origami NGF (DON) affected the growth directionality and spatial capabilities of dorsal root ganglion neurons in culture by introducing a chemotaxis effect along a gradient of functionalized DO structures. Finally, we showed that these elements provide enhanced axonal regeneration in a rat sciatic nerve injury model in vivo. This study is a proof of principle for the functionality of DO in neuronal manipulation and regeneration. The approach proposed here, of an engineered platform formed out of programmable nanoscale elements constructed of DO, could be extended beyond the nervous system and revolutionize the fields of regenerative medicine, tissue engineering, and cell biology.

Original languageEnglish
Article number2300734
JournalBiotechnology Journal
Volume19
Issue number5
DOIs
StatePublished - May 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors. Biotechnology Journal published by Wiley-VCH GmbH.

Keywords

  • DNA origami
  • in-vitro
  • in-vivo
  • neurogenesis
  • neuronal guidance

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