{"title":"DNA origami scaffold promoting nerve guidance and regeneration","authors":"Jonathan Giron, Merav Antman-Passig, Neta Zilony, Hadas Schori, Ido Bachelet, Orit Shefi","doi":"10.1002/biot.202300734","DOIUrl":null,"url":null,"abstract":"<p>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.</p>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biot.202300734","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biotechnology Journal","FirstCategoryId":"5","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/biot.202300734","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
引用次数: 0
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.
将生物元素自组装成生物仿生货物载体以进行靶向和输送是一种很有前景的方法。然而,它仍然面临着实际挑战。我们开发了一种用神经元生长因子(NGF)操纵神经元系统的 DNA 折纸(DO)纳米结构功能化方法。NGF 的生物活性及其与神经元系统的相互作用已在体外和体内模型中得到证实。通过分子自组装制造的 DO 元件通过向细胞表面受体静态呈现配体的空间和时间控制来操纵周围环境。我们的数据显示,它在体外分化 PC12 细胞方面具有有效的生物活性。此外,DNA 折纸 NGF (DON) 通过沿功能化 DO 结构梯度引入趋化效应,影响了培养中背根神经节神经元的生长方向性和空间能力。最后,我们发现这些元素在大鼠坐骨神经损伤模型中增强了轴突再生能力。这项研究证明了 DO 在神经元操作和再生中的功能。这里提出的方法,即由 DO 构建的可编程纳米级元件形成的工程平台,可以扩展到神经系统之外,并为再生医学、组织工程和细胞生物学领域带来革命性的变化。
Biotechnology JournalBiochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
8.90
自引率
2.10%
发文量
123
审稿时长
1.5 months
期刊介绍:
Biotechnology Journal (2019 Journal Citation Reports: 3.543) is fully comprehensive in its scope and publishes strictly peer-reviewed papers covering novel aspects and methods in all areas of biotechnology. Some issues are devoted to a special topic, providing the latest information on the most crucial areas of research and technological advances.
In addition to these special issues, the journal welcomes unsolicited submissions for primary research articles, such as Research Articles, Rapid Communications and Biotech Methods. BTJ also welcomes proposals of Review Articles - please send in a brief outline of the article and the senior author''s CV to the editorial office.
BTJ promotes a special emphasis on:
Systems Biotechnology
Synthetic Biology and Metabolic Engineering
Nanobiotechnology and Biomaterials
Tissue engineering, Regenerative Medicine and Stem cells
Gene Editing, Gene therapy and Immunotherapy
Omics technologies
Industrial Biotechnology, Biopharmaceuticals and Biocatalysis
Bioprocess engineering and Downstream processing
Plant Biotechnology
Biosafety, Biotech Ethics, Science Communication
Methods and Advances.