Blood–brain-barrier-crossing lipid nanoparticles for mRNA delivery to the central nervous system

IF 37.2 1区 材料科学 Q1 CHEMISTRY, PHYSICAL
Chang Wang, Yonger Xue, Tamara Markovic, Haoyuan Li, Siyu Wang, Yichen Zhong, Shi Du, Yuebao Zhang, Xucheng Hou, Yang Yu, Zhengwei Liu, Meng Tian, Diana D. Kang, Leiming Wang, Kaiyuan Guo, Dinglingge Cao, Jingyue Yan, Binbin Deng, David W. McComb, Ramon E. Parsons, Angelica M. Minier-Toribio, Leanne M. Holt, Jiayi Pan, Alice Hashemi, Brian H. Kopell, Alexander W. Charney, Eric J. Nestler, Paul C. Peng, Yizhou Dong
{"title":"Blood–brain-barrier-crossing lipid nanoparticles for mRNA delivery to the central nervous system","authors":"Chang Wang, Yonger Xue, Tamara Markovic, Haoyuan Li, Siyu Wang, Yichen Zhong, Shi Du, Yuebao Zhang, Xucheng Hou, Yang Yu, Zhengwei Liu, Meng Tian, Diana D. Kang, Leiming Wang, Kaiyuan Guo, Dinglingge Cao, Jingyue Yan, Binbin Deng, David W. McComb, Ramon E. Parsons, Angelica M. Minier-Toribio, Leanne M. Holt, Jiayi Pan, Alice Hashemi, Brian H. Kopell, Alexander W. Charney, Eric J. Nestler, Paul C. Peng, Yizhou Dong","doi":"10.1038/s41563-024-02114-5","DOIUrl":null,"url":null,"abstract":"<p>The systemic delivery of mRNA molecules to the central nervous system is challenging as they need to cross the blood–brain barrier (BBB) to reach into the brain. Here we design and synthesize 72 BBB-crossing lipids fabricated by conjugating BBB-crossing modules and amino lipids, and use them to assemble BBB-crossing lipid nanoparticles for mRNA delivery. Screening and structure optimization studies resulted in a lead formulation that has substantially higher mRNA delivery efficiency into the brain than those exhibited by FDA-approved lipid nanoparticles. Studies in distinct mouse models show that these BBB-crossing lipid nanoparticles can transfect neurons and astrocytes of the whole brain after intravenous injections, being well tolerated across several dosage regimens. Moreover, these nanoparticles can deliver mRNA to human brain ex vivo samples. Overall, these BBB-crossing lipid nanoparticles deliver mRNA to neurons and astrocytes in broad brain regions, thereby being a promising platform to treat a range of central nervous system diseases.</p>","PeriodicalId":19058,"journal":{"name":"Nature Materials","volume":"3 1","pages":""},"PeriodicalIF":37.2000,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Materials","FirstCategoryId":"88","ListUrlMain":"https://doi.org/10.1038/s41563-024-02114-5","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}
引用次数: 0

Abstract

The systemic delivery of mRNA molecules to the central nervous system is challenging as they need to cross the blood–brain barrier (BBB) to reach into the brain. Here we design and synthesize 72 BBB-crossing lipids fabricated by conjugating BBB-crossing modules and amino lipids, and use them to assemble BBB-crossing lipid nanoparticles for mRNA delivery. Screening and structure optimization studies resulted in a lead formulation that has substantially higher mRNA delivery efficiency into the brain than those exhibited by FDA-approved lipid nanoparticles. Studies in distinct mouse models show that these BBB-crossing lipid nanoparticles can transfect neurons and astrocytes of the whole brain after intravenous injections, being well tolerated across several dosage regimens. Moreover, these nanoparticles can deliver mRNA to human brain ex vivo samples. Overall, these BBB-crossing lipid nanoparticles deliver mRNA to neurons and astrocytes in broad brain regions, thereby being a promising platform to treat a range of central nervous system diseases.

Abstract Image

求助全文
约1分钟内获得全文 求助全文
来源期刊
Nature Materials
Nature Materials 工程技术-材料科学:综合
CiteScore
62.20
自引率
0.70%
发文量
221
审稿时长
3.2 months
期刊介绍: Nature Materials is a monthly multi-disciplinary journal aimed at bringing together cutting-edge research across the entire spectrum of materials science and engineering. It covers all applied and fundamental aspects of the synthesis/processing, structure/composition, properties, and performance of materials. The journal recognizes that materials research has an increasing impact on classical disciplines such as physics, chemistry, and biology. Additionally, Nature Materials provides a forum for the development of a common identity among materials scientists and encourages interdisciplinary collaboration. It takes an integrated and balanced approach to all areas of materials research, fostering the exchange of ideas between scientists involved in different disciplines. Nature Materials is an invaluable resource for scientists in academia and industry who are active in discovering and developing materials and materials-related concepts. It offers engaging and informative papers of exceptional significance and quality, with the aim of influencing the development of society in the future.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信