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糖基印迹纳米粒子作为人工中和抗体,可有效识别和抑制 HIV-1。

Glycan-Imprinted Nanoparticle as Artificial Neutralizing Antibody for Efficient HIV-1 Recognition and Inhibition.

机构信息

Center for Supramolecular Chemical Biology, National Engineering Laboratory of AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin 130012, China.

CAS Key Laboratory of Separation Sciences for Analytical Chemistry, National Chromatographic R&A Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences Dalian, Liaoning 116023, China.

出版信息

Nano Lett. 2024 Apr 17;24(15):4423-4432. doi: 10.1021/acs.nanolett.4c00142. Epub 2024 Apr 3.

DOI:10.1021/acs.nanolett.4c00142
PMID:38568019
Abstract

The HIV-1 envelope is a heavily glycosylated class 1 trimeric fusion protein responsible for viral entry into CD4 immune cells. Developing neutralizing antibodies against the specific envelope glycans is an alternative method for antiviral therapies. This work presents the first-ever development and characterization of artificial neutralizing antibodies using molecular imprinting technology to recognize and bind to the envelope protein of HIV-1. The prepared envelope glycan-imprinted nanoparticles (GINPs) can successfully prevent HIV-1 from infecting target cells by shielding the glycans on the envelope protein. experiments showed that GINPs have strong affinity toward HIV-1 (K = 36.7 ± 2.2 nM) and possess high anti-interference and specificity. GINPs demonstrate broad inhibition activity against both tier 1 and tier 2 HIV-1 strains with a pM-level IC and exhibit a significant inhibitory effect on long-term viral replication by more than 95%. The strategy provides a promising method for the inhibition and therapy of HIV-1 infection.

摘要

HIV-1 包膜是一种高度糖基化的 I 类三聚体融合蛋白,负责病毒进入 CD4 免疫细胞。开发针对特定包膜糖基的中和抗体是抗病毒治疗的一种替代方法。本工作首次利用分子印迹技术开发和表征了识别和结合 HIV-1 包膜蛋白的人工中和抗体。制备的包膜糖印迹纳米颗粒(GINP)可通过屏蔽包膜蛋白上的糖基成功阻止 HIV-1 感染靶细胞。实验表明,GINP 对 HIV-1 具有很强的亲和力(K = 36.7 ± 2.2 nM),具有高抗干扰性和特异性。GINP 对 I 型和 II 型 HIV-1 株均具有广泛的抑制活性,IC 为 pM 级,并能显著抑制病毒复制超过 95%。该策略为 HIV-1 感染的抑制和治疗提供了一种有前景的方法。

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