苏州大学苏州纳米科技协同创新中心功能纳米与软材料研究所殷黎晨团队在研究中取得进展。他们的最新研究提出了螺旋保护分子夹用于清除无细胞DNA和治疗系统性红斑狼疮。2025年2月11日，国际知名学术期刊《美国化学会杂志》发表了这一成果。

受生物大分子通过空间匹配的自然识别机制的启发，课题组研究人员在此开发了一个树状聚合物模板化、球形、α-螺旋和富含胍的多肽库作为cfDNA清除的分子片段。通过对树突表面多肽长度和密度的优化，确定了性能最好的G3-8，它可以将cfDNA紧密地限制在相邻的棒状α-螺旋之间的空腔内。与它们一样，螺旋状的G3-8而不是随机卷曲的类似物D，L-G3-8在富含血清的条件下使小鼠cfDNA清除，从而抑制TLR9的激活和炎症。在SLE小鼠中，静脉注射。注射G3-8通过清除cfDNA有效预防器官衰竭和抑制炎症。这项研究为稳定结合和清除cfDNA提供了一种开明的策略，并可能改变目前SLE管理的模式。

据了解，无细胞DNA （cfDNA）诱导的免疫紊乱是系统性红斑狼疮（SLE）的发病和恶化的原因。清除cfDNA主题阳离子聚合物代表了一种有前途的SLE管理模式。然而，它们主要通过静电相互作用结合cfDNA，这将导致捕获的cfDNA在被带负电荷的血清/细胞内成分竞争性取代时不希望的放电。

附：英文原文

Title: Helix-Guarded Molecular Clips for Cell-Free DNA Scavenging and Treatment of Systemic Lupus Erythematosus

Author: Yang Zhou, Huan Ye, Yi Yu, Chenglong Ge, Mengyuan Yin, Zhongmin Liu, Jingrui Shen, Renxiang Zhou, Youyong Li, Kam W. Leong, Lichen Yin

Issue&Volume: February 11, 2025

Abstract: Immune disorders induced by cell-free DNA (cfDNA) account for the incidence and deterioration of systemic lupus erythematosus (SLE). Scavenging of cfDNA using cationic polymers represents a promising modality for SLE management. However, they bind cfDNA mainly via electrostatic interaction, which would result in an undesired discharge of the captured cfDNA upon competitive replacement by the negatively charged serum/intracellular components. Inspired by the natural recognition mechanism of biomacromolecules via spatial matching, we herein developed a library of dendrimer-templated, spherical, α-helical, and guanidine-rich polypeptides as molecular clips for cfDNA scavenging. Upon optimization of the polypeptide length and density on the dendrimer surface, the top-performing G3-8 was identified, which could tightly confine cfDNA within the cavity between the adjacent, rod-like α-helices. As thus, the helical G3-8 but not the random-coiled analogue _D,L-G3-8 enabled robust cfDNA scavenging under serum-rich conditions to inhibit TLR9 activation and inflammation. In SLE mice, i.v. injected G3-8 efficiently prevented organ failure and inhibited inflammation by scavenging cfDNA. This study provides an enlightened strategy to stably bind and scavenge cfDNA and may shift the current paradigm of SLE management.

DOI: 10.1021/jacs.4c15646

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c15646