资料：Enhanced mRNA delivery using ultrasound-delivered click reactive anchors作家：Emilio Di Ianni, Jueun Jeon, Huiyu Hu, Jeremy M. Quintana, Chanseo Lee, Edwina Abou Haidar, Sedra Mohammadi, Ayrton Zargani-Piccardi, Mohammed Mahamdeh, Iván Coto Hernández, Thomas S.C. Ng, Koen Breyne, Hakho Lee, Xandra O. Breakefield, Miles A. Miller医学文献外链：//www.biorxiv.org/content/10.1101/2025.01.28.635330v1.abstract前言：Therapeutic nucleic acid delivery has many potential applications, but it remains challenging to target extrahepatic tissues in a flexible and image-guided manner. To address this issue, we report a bioorthogonal pre-targeting strategy that uses focused ultrasound to promote the delivery of mRNA-loaded lipid nanoparticles (mRNA-LNP). We synthesized amphiphilic click reactive anchors (ACRAs) consisting of a phospholipid PEG-conjugate functionalized with transcyclooctene (TCO) or its companion reactive partner methyltetrazine (mTz), yielding ACRA-TCO and ACRA-mTz. ACRA derivatives were screened for cellular activity, yielding functionalized DOPE-PEG (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N- (polyethylene glycol)) derivatives outperforming those containing saturated lipid or branched PEG. Nanobubbles encapsulating ultrasound-responsive gas precursor delivered ACRA-TCO to targeted cells and tissues using focused ultrasound, and this pre-targeting promoted the subsequent delivery of mRNA- LNP functionalized with companion ACRA-mTz. In cell cultures and in mice, ultrasound pre-targeting enhanced the accumulation of mTz-functionalized small molecule and nanoparticle compounds by 75% and 3.6-fold, respectively, and increased gene expression using mRNA-LNP in vivo. Taken together, this report presents a modular, ultrasound-enabled strategy for enhancing nucleic acid delivery in targeted tissues.

某种生物制品正交预靶向疗法思路，该思路利于精准定位超音波有利于载mRNA的脂质纳米技术粉末（mRNA-LNP）的递送。我们都合出了两亲选择体现锚（ACRA），其由磷脂PEG共轭物构成的，该共轭物用反式环辛烯（TCO）或其牵动体现性配体甲基四嗪（mTz）功能性化，以此导出ACRA-TCO和ACRA-mTz。对ACRA双重性物制品参与了人体细胞活性酶挑选，然而知道性能指标化的DOPE-PEG（1,2-二油酰-sn-甘油-3-磷酸酒精胺-N-（聚乙二醇））诞生物的性能指标依赖于含带供大于求脂质或支链PEG的诞生物。納米应用气泡包装mri卡死废气前体，应用把握mri将ACRA-TCO递送往要求内部和安排，这一预靶向药物使用利于了接着递送经ACRA-mTz性能指标化的mRNA-LNP。在细胞膜激发物和小鼠肚子里，多普勒彩超预靶向治疗目的区别使mTz功用化的小氧分子和纳米级粒状有机物的积累更多新增了75%和3.6倍，并提升了mRNA-LNP在肚子里的人类基因描述。阐明阐明，本情况汇报给出半个种模组化、多普勒彩超颠覆性创新的对策，适用怎强核酸在计划组识中的递送。各种相关举荐：DSPE-PEG-ProgestroneDSPE-PEG-RGDDSPE-PEG-SCDSPE-PEG-SCMDSPE-PEG-SGDSPE-PEG-SHDSPE-PEG-SilaneDSPE-PEG-SP2-AADSPE-PEG-SSDSPE-PEG-TCODSPE-PEG-Tetrazine往上文章內容內容来原当下刊物或论文参考文献，此事侵权案请取得联系公司册除！