Lyophilization enables thermostable formulation of dengue virus-derived defective interfering particles

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

Antiviral research Pub Date : 2025-12-01 Epub Date: 2025-11-08 DOI:10.1016/j.antiviral.2025.106308

Min-Hsuan Lin , Pramila Maniam , Bing Tang , David Harrich

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引用次数: 0

Abstract

Defective interfering particles (DIPs), containing truncated defective viral genomes (DVGs), are natural byproducts of RNA virus replication with potent antiviral activity. We recently developed a virus-free, dengue virus (DENV)-based platform producing antiviral DIPs with DI290 DVG, termed DIP-DI290. In this study, we established a scalable purification and lyophilization workflow for creating thermostable DIP-DI290 formulations for long-term storage. DIP-DI290 particles were purified via tangential flow filtration and ceramic hydroxyapatite chromatography, then lyophilized and reconstituted for biological assessment. After three months of storage at −80 °C, 4 °C, or room temperature, reconstituted DIP-DI290 retained biological activity, significantly upregulating interferon-stimulated genes (ISGs) and suppressing DENV-2 replication. These findings demonstrate that lyophilization preserves DIP-DI290's antiviral efficacy across diverse storage conditions, supporting its development as a thermostable, field-deployable therapeutic platform for virus infections.

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冻干使登革病毒衍生的缺陷干扰颗粒的热稳定性配方成为可能。

含有截断缺陷病毒基因组（dvg）的缺陷干扰颗粒（dip）是RNA病毒复制的天然副产物，具有强大的抗病毒活性。我们最近开发了一种无病毒、基于登革热病毒（DENV）的平台，生产含有DI290 DVG的抗病毒dip，称为DIP-DI290。在这项研究中，我们建立了一个可扩展的纯化和冻干工作流程，用于创建长期储存的耐热DIP-DI290配方。DIP-DI290颗粒经切向流过滤和陶瓷羟基磷灰石层析纯化，然后冻干重组用于生物学评价。在-80°C、4°C或室温下保存三个月后，重组DIP-DI290保留了生物活性，显著上调干扰素刺激基因（ISGs）并抑制DENV-2复制。这些研究结果表明，冻干保存DIP-DI290在不同储存条件下的抗病毒功效，支持其作为耐热、可现场部署的病毒感染治疗平台的发展。

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

Antiviral research 医学-病毒学

CiteScore

17.10

自引率

3.90%

发文量

157

审稿时长

34 days

期刊介绍： Antiviral Research is a journal that focuses on various aspects of controlling viral infections in both humans and animals. It is a platform for publishing research reports, short communications, review articles, and commentaries. The journal covers a wide range of topics including antiviral drugs, antibodies, and host-response modifiers. These topics encompass their synthesis, in vitro and in vivo testing, as well as mechanisms of action. Additionally, the journal also publishes studies on the development of new or improved vaccines against viral infections in humans. It delves into assessing the safety of drugs and vaccines, tracking the evolution of drug or vaccine-resistant viruses, and developing effective countermeasures. Another area of interest includes the identification and validation of new drug targets. The journal further explores laboratory animal models of viral diseases, investigates the pathogenesis of viral diseases, and examines the mechanisms by which viruses avoid host immune responses.