将 mRNA 与 PBS 和钙离子结合可提高 mRNA 转染肿瘤的效率

IF 6.5 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Molecular Therapy. Nucleic Acids Pub Date : 2024-07-17 DOI:10.1016/j.omtn.2024.102273

Noriko Ohta, Takashi Matsuzaki, Masayoshi Nakai, Yasuhiko Tabata, Keisuke Nimura

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引用次数: 0

摘要

mRNA 是一种很有前景的蛋白质表达方式。要将 mRNA 有效转染到细胞中，需要药物输送系统。在这项研究中，我们评估了几种将 mRNA 转染到肿瘤中的药物递送系统。一种脂质纳米颗粒能将 mRNA 运送到引流淋巴结和肝脏，甚至通过瘤内注射也能做到。基于脂质体的系统并不能持续为不同类型的肿瘤细胞提供 mRNA。我们发现，PBS 能将 mRNA 导入多种肿瘤，而钙离子能提高效率，尤其是在雄性小鼠中。圆二色性光谱仪表明，PBS 中的 mRNA 结构发生了变化。透射电子显微镜显示，钙离子促进了 PBS 中 mRNA 纳米颗粒的形成。用 PBS + 钙离子转染编码 OX40-配体、白细胞介素（IL）-36γ 和 IL-23 的 mRNA 可抑制肿瘤生长。我们的研究结果表明，将 PBS 与钙离子结合可促进 mRNA 转染到肿瘤中。这些数据为开发用于癌症治疗的 mRNA 转染方法提供了信息。

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Combining mRNA with PBS and calcium ions improves the efficiency of the transfection of mRNA into tumors

mRNA is a promising modality for expressing a protein . Drug delivery systems are required for the efficient transfection of mRNA into cells. In this study, we evaluated several drug delivery systems for transfecting mRNA into tumors. A lipid nanoparticle delivered mRNA to the draining lymph nodes and liver, even by intratumoral injection. A liposome-based system did not consistently provide mRNA for different types of tumor cells. We found that PBS introduced mRNA into several tumors, and calcium ions enhanced the efficiency, particularly in male mice. The circular dichroism spectrometer suggested a structural change in mRNA in PBS. Transmission electron microscopy revealed that calcium ions promoted the formation of mRNA nanoparticles in PBS. Transfection of mRNAs coding OX40-ligand, interleukin (IL)-36γ, and IL-23 by PBS + calcium ions attenuated tumor growth. Our results indicate that combining PBS with calcium ions promotes the transfection of mRNA into tumors. These data provide information for the development of methods for transfection of mRNA for cancer therapy.

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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.