Systemic RNAi-mediated Gene Silencing in Nonhuman Primate and Rodent Myeloid Cells
Name
1-s2.0-S2162253116300610-main.pdf
Description
Published version
Size
2.15 MB
Format
Adobe PDF
Checksum (MD5)
0579e4cf3773a3d0dd3f927a1fbd9e77
Author(s)
Novobrantseva, Tatiana I
Borodovsky, Anna
Wong, Jamie
Klebanov, Boris
Zafari, Mohammad
Yucius, Kristina
Querbes, William
Ge, Pei
Ruda, Vera M
Milstein, Stuart
Date Issued
2012
Journal
Molecular Therapy Nucleic Acids
Publisher
Elsevier BV
Citation
Novobrantseva, Tatiana I et al. "Systemic RNAi-mediated Gene Silencing in Nonhuman Primate and Rodent Myeloid Cells." Molecular Therapy 1 (2012): e4 © 2012 American Society of Gene and Cell Therapy
Version
Final published version
Abstract
Leukocytes are central regulators of inflammation and the target cells of therapies for key diseases, including autoimmune, cardiovascular, and malignant disorders. Efficient in vivo delivery of small interfering RNA (siRNA) to immune cells could thus enable novel treatment strategies with broad applicability. In this report, we develop systemic delivery methods of siRNA encapsulated in lipid nanoparticles (LNP) for durable and potent in vivo RNA interference (RNAi)-mediated silencing in myeloid cells. This work provides the first demonstration of siRNA-mediated silencing in myeloid cell types of nonhuman primates (NHPs) and establishes the feasibility of targeting multiple gene targets in rodent myeloid cells. The therapeutic potential of these formulations was demonstrated using siRNA targeting tumor necrosis factor-α (TNFα) which induced substantial attenuation of disease progression comparable to a potent antibody treatment in a mouse model of rheumatoid arthritis (RA). In summary, we demonstrate a broadly applicable and therapeutically relevant platform for silencing disease genes in immune cells. Keywords: delivery; immune cell; siRNA
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Harvard University--MIT Division of Health Sciences and Technology
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/mtna.2011.3
