In Vivo RNA Delivery to Hematopoietic Stem and Progenitor Cells via Targeted Lipid Nanoparticles
Name
shi-et-al-2023-in-vivo-rna-delivery-to-hematopoietic-stem-and-progenitor-cells-via-targeted-lipid-nanoparticles.pdf
Description
Published version
Size
2.83 MB
Format
Adobe PDF
Checksum (MD5)
b0ef081e95165400dddf185bd293649c
Author(s)
Shi, Dennis
Toyonaga, Sho
Anderson, Daniel G
Date Issued
April 12, 2023
Journal
Nano Letters
Publisher
American Chemical Society
Citation
Dennis Shi, Sho Toyonaga, and Daniel G. Anderson Nano Letters 2023 23 (7), 2938-2944.
Version
Final published version
Abstract
Ex vivo autologous hematopoietic stem cell (HSC) gene therapy has provided new therapies for the treatment of hematological disorders. However, these therapies have several limitations owing to the manufacturing complexities and toxicity resulting from required conditioning regimens. Here, we developed a c-kit (CD117) antibody-targeted lipid nanoparticle (LNP) that, following a single intravenous injection, can deliver RNA (both siRNA and mRNA) to HSCs in vivo in rodents. This targeted delivery system does not require stem cell harvest, culture, or mobilization of HSCs to facilitate delivery. We also show that delivery of Cre recombinase mRNA at a dose of 1 mg kg-1 can facilitate gene editing to almost all (∼90%) hematopoietic stem and progenitor cells (HSPCs) in vivo, and edited cells retain their stemness and functionality to generate high levels of edited mature immune cells.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1021/acs.nanolett.3c00304
