RNAi delivery mediated by milk extracellular vesicles in colon cancer.

IF 6.1 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Molecular Therapy. Nucleic Acids Pub Date : 2025-07-31 eCollection Date: 2025-09-09 DOI:10.1016/j.omtn.2025.102644

Jessie Santoro, Silvia Nuzzo, Andrea Soricelli, Marco Salvatore, Anna Maria Grimaldi

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引用次数: 0

Abstract

Small interfering RNA (siRNA) has emerged as a powerful tool for gene silencing, offering great potential for therapeutic applications. However, the clinical use of siRNA is limited by several challenges, including poor stability in biological fluids, off-target effects, and toxicity due to non-specific cellular uptake. To address these limitations, extracellular vesicles (EVs) derived from milk are being investigated as natural carriers to deliver siRNA and microRNA. These EVs offer advantages such as low immunogenicity, biocompatibility, and the ability to cross biological barriers. Here, we optimized methods for loading siRNA into milk-derived EVs (mEVS) and assessed their ability to protect siRNA from degradation while preserving its gene-silencing efficacy. We targeted a potential biomarker, Aurora kinase A (AURKA), known to be deregulated in many types of solid tumors, including colon cancer. Our results demonstrate that mEVs-loaded siRNA retains the stability and functionality of internalized siRNA, leading to efficient gene silencing in target cells. This approach highlights the potential of mEVs as a safe and valuable delivery system, overcoming key limitations of siRNA therapeutics and opening new avenues and opening new avenues for diagnostic and therapeutic strategies in colon cancer.

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乳细胞外囊泡介导的结肠癌RNAi传递。

小干扰RNA （siRNA）已成为基因沉默的有力工具，具有巨大的治疗应用潜力。然而，siRNA的临床应用受到一些挑战的限制，包括在生物液体中的稳定性差、脱靶效应以及由于非特异性细胞摄取而产生的毒性。为了解决这些局限性，人们正在研究从牛奶中提取的细胞外囊泡（ev）作为siRNA和microRNA的天然载体。这些电动汽车具有低免疫原性、生物相容性和跨越生物屏障的能力等优点。在这里，我们优化了将siRNA装载到牛奶衍生ev （mEVS）中的方法，并评估了它们在保护siRNA免受降解的同时保持其基因沉默功效的能力。我们的目标是一种潜在的生物标志物，极光激酶a (AURKA)，已知在许多类型的实体肿瘤中不受调控，包括结肠癌。我们的研究结果表明，mev负载的siRNA保留了内化siRNA的稳定性和功能，从而在靶细胞中实现了有效的基因沉默。该方法突出了mev作为一种安全且有价值的递送系统的潜力，克服了siRNA治疗方法的关键局限性，为结肠癌的诊断和治疗策略开辟了新的途径和途径。

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

Molecular Therapy. Nucleic Acids MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

15.40

自引率

1.10%

发文量

336

审稿时长

20 weeks

期刊介绍： Molecular Therapy Nucleic Acids is an international, open-access journal that publishes high-quality research in nucleic-acid-based therapeutics to treat and correct genetic and acquired diseases. It is the official journal of the American Society of Gene & Cell Therapy and is built upon the success of Molecular Therapy. The journal focuses on gene- and oligonucleotide-based therapies and publishes peer-reviewed research, reviews, and commentaries. Its impact factor for 2022 is 8.8. The subject areas covered include the development of therapeutics based on nucleic acids and their derivatives, vector development for RNA-based therapeutics delivery, utilization of gene-modifying agents like Zn finger nucleases and triplex-forming oligonucleotides, pre-clinical target validation, safety and efficacy studies, and clinical trials.