Lipid Nanoparticle-mediated MRNA Delivery to CD34 Cells in Rhesus Monkeys.

Details

• Alternative Title:
  Nature Biotechnology, 2025, v. 43, no. 11: Lipid Nanoparticle-mediated MRNA Delivery to CD34 Cells in Rhesus Monkeys.
• Journal Article:
  Nature Biotechnology
• Personal Author:
  Kim, Hyejin ; Zenhausern, Ryan ; Gentry, Kara ; Lian, Liming ; Huayamares, Sebastian G. ; Radmand, Afsane ; Loughrey, David ; Podilapu, Ananda ; Hatit, Marine Z.C. ; Ni, Huanzhen ; Li, Andrea ; Shajii, Aram ; Peck, Hannah E. ; Han, Keyi ; Hua, Xuanwen ; Jia, Shu ; Martinez, Michele ; Lee, Charles ; Santangelo, Philip J. ; Tarantal, Alice ; Dahlman, James E.
• Description:
  Transplantation of ex vivo engineered hematopoietic stem cells (HSCs) can lead to robust clinical responses but carries risks of adverse events from bone marrow mobilization, chemotherapy conditioning and other factors. HSCs have been modified in vivo using lipid nanoparticles (LNPs) decorated with targeting moieties, which increases manufacturing complexity. Here we screen 105 LNPs without targeting ligands for effective homing to the bone marrow in mouse. We report an LNP named LNP
  
  that delivers mRNA to murine HSCs in vivo, primary human HSCs ex vivo and CD34
  
  cells in rhesus monkeys (Macaca mulatta) in vivo at doses of 0.25 and 0.4 mg kg
  
  . Without mobilization and conditioning, LNP
  
  can mediate delivery of mRNA to HSCs and their progenitor cells (HSPCs), as well as to the liver in rhesus monkeys, without serum cytokine activation. These data support the hypothesis that in vivo delivery to HSCs and HSPCs in nonhuman primates is feasible without targeting ligands.
• Content Notes:
  Author manuscript
• Subjects:
  • Animals
  • Macaca mulatta
  • Nanoparticles
  • Humans
  • Hematopoietic Stem Cells
  • Antigens, CD34
  • Mice
  • Lipids
  • RNA, Messenger
  • Hematopoietic Stem Cell Transplantation
  More +
• Source:
  Nature Biotechnology, 2025, v. 43, no. 11
• DOI:
  https://doi.org/10.1038/s41587-024-02470-2
• ISSN:
  1087-0156 ; 1546-1696
• Pubmed ID:
  39578569
• Pubmed Central ID:
  PMC12095617
• Document Type:
  Text
• Funding:
  UH3 TR002855/TR/NCATS NIH HHSUnited States/ ; P51 OD011107/OD/NIH HHSUnited States/ ; TL1 DK136047/DK/NIDDK NIH HHSUnited States/ ; UL1 TR002378/TR/NCATS NIH HHSUnited States/ ; UH3-TR002855/Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; U42 OD027094/CD/ODCDC CDC HHSUnited States/ ; P51-OD011107/Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; TL1DK136047/Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; UG3 TR002855/TR/NCATS NIH HHSUnited States/ ; U42 OD027094/OD/NIH HHSUnited States/
• Genre:
  Journal Article
• Pages in Document:
  1813-1820 (25 pdf pages)
• Volume:
  43
• Issue:
  11
• Download URL:
  https://stacks.cdc.gov/view/cdc/261909/cdc_261909_DS1.pdf
• File Type:
  [PDF - 1.91 MB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:f29a438151fbac7d61abf5079b187c40121d32d1a7a88a5158a03457b6bdc5b0b7fa99cb117cefee0ba61239beef0ddb6600ea973a86f1c9bf05a340a66fda7c