2. Academic Validation
  3. Lipid Nanoparticles Enhance mRNA Delivery to the Central Nervous System Upon Intrathecal Injection

Lipid Nanoparticles Enhance mRNA Delivery to the Central Nervous System Upon Intrathecal Injection

  • Adv Mater. 2025 Jul;37(27):e2417097. doi: 10.1002/adma.202417097.
Yonger Xue 1 2,  Chang Wang 1 2,  Haoyuan Li 1,  Shi Du 2,  Yichen Zhong 1 2,  Yuebao Zhang 1,  Siyu Wang 1,  Kaiyuan Guo 1,  Xucheng Hou 1,  Diana D Kang 1 2,  Zhengwei Liu 1,  Meng Tian 1,  Dinglingge Cao 1,  Binbin Deng 3,  David W McComb 3 4,  Tamara Markovic 5,  Jiayi Pan 6,  Mandana Borna 6,  Eric J Nestler 5,  Paul C Peng 7,  Yizhou Dong 2 8
Affiliations

Affiliations

  • 1 Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • 2 Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, 43210, USA.
  • 3 Center for Electron Microscopy and Analysis, The Ohio State University, Columbus, OH, 43212, USA.
  • 4 Department of Materials Science and Engineering, The Ohio State University, Columbus, OH, 43210, USA.
  • 5 Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • 6 Biogen Inc, 225 Binney Street, Cambridge, MA, 02142, USA.
  • 7 City Therapeutics, 399 Binney Street, Cambridge, MA, 02142, USA.
  • 8 Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Biomedical Engineering and Imaging Institute, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
PMID: 40317512 DOI: 10.1002/adma.202417097
Abstract

Lipid nanoparticle-messenger RNA formulations have garnered significant attention for their therapeutic potential in infectious diseases, Cancer and genetic disorders. However, effective mRNA delivery to the central nervous system (CNS) remains a formidable challenge. To overcome this limitation, a class of brain-targeting lipids (BLs) is developed by incorporating brain-targeting small molecules with amino lipids and formulated them with helper lipids to generate brain-targeting lipid nanoparticles (BLNPs) for mRNA delivery. Screening studies led to a lead formulation, TD5 BLNPs, outperforming FDA-approved DLin-MC3-DMA LNPs in delivering mRNA to the brain upon intrathecal injection. Specifically, a single intrathecal injection of TD5 BLNP-GFP mRNA led to GFP expression in 29.6% of neurons and 38.1% of astrocytes across the brain. In an Ai14 mouse model, TD5 BLNP-Cre recombinase mRNA treatment induced tdTomato expression in ≈30% of neurons and 40% of astrocytes across major brain regions. Notably, delivery of Cas9 mRNA/sgRNA complex using TD5 BLNPs achieved effective genome editing in the brain. Additionally, TD5 BLNPs showed comparable safety profiles to MC3 LNPs, indicating promising biocompatibility. Overall, this TD5 BLNP formulation effectively delivers mRNA to brain tissues via intrathecal injection and facilitates efficient expression in both neurons and astrocytes, presenting a potential strategy for treating CNS diseases.

Keywords

central nervous system; intrathecal injection; lipid nanoparticles; mRNA.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z