Transfection of unmodified oligodeoxynucleotide with polyethylenimine reduces the level of hepatitis B surface antigen.

IF 4 2区生物学 Q2 MICROBIOLOGY

Frontiers in Microbiology Pub Date : 2025-05-01 eCollection Date: 2025-01-01 DOI:10.3389/fmicb.2025.1600679

Junyu Lin, Jing Li

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Abstract

Introduction: The delivery of nucleic acid into cells using polyethylenimine (PEI) as non-viral carrier is a potential candidate technique for the treatment of hepatitis B virus (HBV) infection.

Methods: In the present study, PEI was used as cationic polymers and transfected with unmodified oligodeoxynucleotides in cell cultures and the BALB/c mouse model to investigate its efficiency in blocking HBV surface antigen (HBsAg) secretion.

Results and discussion: PEI/oligonucleotide complexes selectively inhibited HBsAg secretion in the culture supernatant, while there were no evident alterations in HBeAg and HBV DNA levels, thereby suggesting its potential inhibitory activity against the production of HBsAg. The complexes formed by PEI with double-stranded decoy oligonucleotides also suppressed HBsAg secretion but showed no expected interference with the intermediate levels of HBV transcription or replication. Furthermore, PEI/plasmid-DNA complexes demonstrated no influence on the expression levels of HBsAg, thus highlighting the specific effects of PEI/oligonucleotides exerted on HBsAg release. PEI-oligonucleotides transfection prior to the viral inoculation impaired HBV infection in HepG2-NCTP cells. Importantly, the PEI/oligonucleotide complex also induced the decline of HBsAg in hydrodynamically injected BALB/c mice. These findings demonstrate that transfection of PEI/oligonucleotide complexes can help effectively reduce HBsAg level and may offer a new potential avenue for the development of anti-HBV treatment.

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用聚乙烯亚胺转染未修饰的寡脱氧核苷酸可降低乙型肝炎表面抗原的水平。

简介：利用聚乙烯亚胺（PEI）作为非病毒载体将核酸送入细胞是治疗乙型肝炎病毒（HBV）感染的潜在候选技术。方法：在本研究中，PEI作为阳离子聚合物，在细胞培养和BALB/c小鼠模型中转染未经修饰的寡脱氧核苷酸，以研究其阻断HBV表面抗原（HBsAg）分泌的效率。结果与讨论：PEI/寡核苷酸复合物选择性抑制培养上清中HBsAg的分泌，而HBeAg和HBV DNA水平无明显变化，提示其对HBsAg的产生具有潜在的抑制作用。PEI与双链诱饵寡核苷酸形成的复合物也抑制HBsAg分泌，但对HBV转录或复制的中间水平没有预期的干扰。此外，PEI/质粒dna复合物对HBsAg的表达水平没有影响，从而突出了PEI/寡核苷酸对HBsAg释放的特异性作用。在病毒接种前转染pei寡核苷酸可损害HepG2-NCTP细胞的HBV感染。重要的是，PEI/寡核苷酸复合物也诱导了水动力注射BALB/c小鼠HBsAg的下降。这些发现表明转染PEI/寡核苷酸复合物可以有效降低HBsAg水平，并可能为开发抗hbv治疗提供新的潜在途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Microbiology MICROBIOLOGY-

CiteScore

7.70

自引率

9.60%

发文量

4837

审稿时长

14 weeks

期刊介绍： Frontiers in Microbiology is a leading journal in its field, publishing rigorously peer-reviewed research across the entire spectrum of microbiology. Field Chief Editor Martin G. Klotz at Washington State University is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.