殷黎晨教授及其合作者在Adv. Mater.上发表论文

作者：

Xun Liu^1,2#, Ziyin Zhao^2#, Wei Li^2#, Mengyao Ren², Haoyu Zhang², Desheng Cao², Yehan Wang², He Yang¹, Yajie Li²,Manhui Zhu⁴, Laiqing Xie³*, and Lichen Yin²*

单位：

¹Department of Thoracic Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215004 China.

²Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory of Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, 215123 China.

³Department of Ophthalmology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004 China.

⁴Department of Ophthalmology, Lixiang Eye Hospital of Soochow University, Suzhou, 215123 China.

摘要：

Ribonucleoprotein (RNP)-based CRISPR/Cas9 genome editing holds great potential for the treatment of choroidal neovascularization (CNV), which however, is challenged by the lack of efficient cytosolic protein delivery tools. Herein, reversibly-phosphorylated pro-proteins (P-proteins) with conjugated adenosine triphosphate (ATP) tags are engineered and coupled with a membrane-penetrating, guanidine-enriched, α-helical polypeptide (_LGP) to mediate robust and universal cytosolic delivery. _LGP forms salt-stable nanocomplexes (NCs) with P-proteins via electrostatic interaction and salt bridging, and the helix-assisted, strong membrane activities of _LGP enabled efficient cellular internalization and endolysosomal escape of NCs. Therefore, this approach allows efficient cytosolic delivery of a wide range of protein cargoes and maintains their bioactivities due to endolysosomal acidity-triggered traceless restoration of P-proteins. Notably, intravitreally delivered _LGP/P-RNP NCs targeting hypoxia-inducible factor-1α (HIF-1α) induce pronounced gene disruption to downregulate pro-angiogenic factors and alleviate subretinal fibrosis, ultimately provoking robust therapeutic efficacy in CNV mice. Such a facile and versatile platform provides a powerful tool for cytosolic protein delivery and genome editing, and it holds promising potential for the treatment of CNV-associated diseases, such as age-related macular degeneration.

影响因子：

27.4

分区情况：

一区

链接：

https://doi.org/10.1002/adma.202412366