利用α -糖醛酸结合肽修饰的脂质纳米颗粒将mRNA传递到杜氏肌营养不良模型小鼠的肌肉中。

IF 1.7 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Eri Sasaki, Yuki Itaya, Yoko Endo-Takahashi, Yusuke Yano, Nobuhito Hamano, Keisuke Hamada, Yamato Kikkawa, Kosuke Nakashima, Rui Tada, Tsuyoshi Miura, Hiroki Tanaka, Hidetaka Akita, Motoyoshi Nomizu, Yoichi Negishi
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引用次数: 0

摘要

杜氏肌营养不良症(DMD)是一种遗传性疾病,需要基因或核酸治疗,这涉及到肌肉靶向递送治疗物质。我们先前使用A2G80肽开发了针对DMD模型小鼠(mdx)肌肉组织的脂质体,该肽与肌细胞膜上大量表达的α-肌营养不良聚糖具有亲和力。然而,这些脂质体不携带基因或核酸。在这项研究中,我们旨在开发肌肉靶向脂质纳米颗粒(LNPs)包裹荧光素酶mRNA,并评估这些LNPs全身给药后的基因表达水平。我们首先利用聚乙二醇(PEG)-二豆脂酰甘油(DMG)和聚乙二醇-二硬脂酰甘油(DSG)在mdx系统给药中评估了基于荧光素酶活性的mRNA递送效率。与PEG-DMG-LNPs相比,PEG-DSG-LNPs在肝脏和脾脏中的荧光素酶表达较低,而在mdx肌肉组织中的表达较高。使用PEG-DSG将A2G80肽添加到LNPs中(A2G80- dsg -LNPs)可显著增加其在mdx中的活性,但在正常小鼠中没有。这些结果表明,A2G80-DSG-LNPs允许肌肉靶向mRNA递送,是治疗DMD的有用工具。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Systemic mRNA Delivery into the Muscle of Duchenne Muscular Dystrophy Model Mice Using Alpha-Dystroglycan Binding Peptide Modified Lipid Nanoparticles.

Duchenne muscular dystrophy (DMD) is a hereditary disease that requires gene or nucleic acid therapy, which involves muscle-targeted delivery of therapeutic material. We previously developed liposomes targeting muscle tissue in DMD model mice (mdx) using an A2G80 peptide, which has an affinity for α-dystroglycan abundantly expressed on the muscle cell membrane. However, these liposomes did not carry gene or nucleic acids. In this study, we aimed to develop muscle-targeting lipid nanoparticles (LNPs) encapsulating luciferase mRNA and evaluate gene expression levels after systemic administration of these LNPs. We first evaluated the efficiency of mRNA delivery based on luciferase activity using polyethylene glycol (PEG)-dimyristoyl glycerol (DMG) and PEG-distearoyl glycerol (DSG) in mdx systemic administration. PEG-DSG-LNPs showed lower luciferase expression in the liver and spleen and higher expression in mdx muscle tissue than PEG-DMG-LNPs. The addition of the A2G80 peptide to LNPs using PEG-DSG (A2G80-DSG-LNPs) significantly increased their activity in mdx but not in normal mice. These results suggest that A2G80-DSG-LNPs allow for muscle-targeted mRNA delivery and are useful tools for DMD treatment.

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来源期刊
CiteScore
3.50
自引率
5.00%
发文量
247
审稿时长
2 months
期刊介绍: Biological and Pharmaceutical Bulletin (Biol. Pharm. Bull.) began publication in 1978 as the Journal of Pharmacobio-Dynamics. It covers various biological topics in the pharmaceutical and health sciences. A fourth Society journal, the Journal of Health Science, was merged with Biol. Pharm. Bull. in 2012. The main aim of the Society’s journals is to advance the pharmaceutical sciences with research reports, information exchange, and high-quality discussion. The average review time for articles submitted to the journals is around one month for first decision. The complete texts of all of the Society’s journals can be freely accessed through J-STAGE. The Society’s editorial committee hopes that the content of its journals will be useful to your research, and also invites you to submit your own work to the journals.
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