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Supramolecular Peptide Nanofibrils with Optimized Sequences and Molecular Structures for Efficient Retroviral Transduction
ChemRxiv Pub Date : 2020-10-23
Stefanie Sieste, Thomas Mack, Edina Lump, Manuel Hayn, Desiree Schütz, Annika Röcker, Christoph Meier, Frank Kirchhoff, Tuomas Knowles, Francesco S. Ruggeri, Christopher Synatschke, Jan Münch, Tanja Weil

Amyloid-like peptide nanofibrils (PNFs) are abundant in nature providing rich bioactivities and playing both functional and pathological roles. The structural features responsible for their unique bioactivities are, however, still elusive. Supramolecular nanostructures are notoriously challenging to optimize, as sequence changes affect self-assembly, fibril morphologies and biorecognition. Herein, we report the first sequence optimization of PNFs for enhanced retroviral gene transduction via a multiparameter and a multiscale approach. Retroviral gene transfer is the method of choice for stable delivery of genetic information into cells offering great perspectives for the treatment of genetic disorders. Single fibril imaging, zeta potential, vibrational spectroscopy and quantitative retroviral transduction assays provided the structure parameters responsible for PNF assembly, fibril morphologies and PNF-virus-cell interactions. Optimized peptide sequences have been obtained quantitatively forming supramolecular nanofibrils with high intermolecular beta-sheet content that efficiently bound virions and attached to cellular membranes revealing efficient retroviral gene transfer

中文翻译:

具有优化序列和分子结构的高效逆转录病毒转导的超分子肽纳米纤维。

淀粉样蛋白肽纳米原纤维(PNF)性质丰富,可提供丰富的生物活性并同时发挥功能和病理作用。然而,负责其独特的生物活性的结构特征仍然难以捉摸。众所周知,超分子纳米结构难以优化,因为序列变化会影响自组装,原纤维形态和生物识别。在此,我们报告了通过多参数和多尺度方法增强反转录病毒基因转导的PNF的第一个序列优化。逆转录病毒基因转移是将遗传信息稳定传递至细胞的一种选择方法,为治疗遗传疾病提供了广阔的前景。单纤维成像,ζ电势,振动光谱和定量逆转录病毒转导分析提供了负责PNF组装,原纤维形态和PNF-病毒-细胞相互作用的结构参数。已获得定量优化的肽序列,可定量形成具有高分子间β-折叠含量的超分子纳米纤维,可有效结合病毒体并附着在细胞膜上,从而显示有效的逆转录病毒基因转移
更新日期:2020-10-28
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