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Systemic RNAi-mediated Gene Silencing in Nonhuman Primate and Rodent Myeloid Cells

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 app...

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Autores principales: Novobrantseva, Tatiana I, Borodovsky, Anna, Wong, Jamie, Klebanov, Boris, Zafari, Mohammad, Yucius, Kristina, Querbes, William, Ge, Pei, Ruda, Vera M, Milstein, Stuart, Speciner, Lauren, Duncan, Rick, Barros, Scott, Basha, Genc, Cullis, Pieter, Akinc, Akin, Donahoe, Jessica S, Narayanannair Jayaprakash, K, Jayaraman, Muthusamy, Bogorad, Roman L, Love, Kevin, Whitehead, Katie, Levins, Chris, Manoharan, Muthiah, Swirski, Filip K, Weissleder, Ralph, Langer, Robert, Anderson, Daniel G, de Fougerolles, Antonin, Nahrendorf, Matthias, Koteliansky, Victor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3381593/
https://www.ncbi.nlm.nih.gov/pubmed/23344621
http://dx.doi.org/10.1038/mtna.2011.3
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author Novobrantseva, Tatiana I
Borodovsky, Anna
Wong, Jamie
Klebanov, Boris
Zafari, Mohammad
Yucius, Kristina
Querbes, William
Ge, Pei
Ruda, Vera M
Milstein, Stuart
Speciner, Lauren
Duncan, Rick
Barros, Scott
Basha, Genc
Cullis, Pieter
Akinc, Akin
Donahoe, Jessica S
Narayanannair Jayaprakash, K
Jayaraman, Muthusamy
Bogorad, Roman L
Love, Kevin
Whitehead, Katie
Levins, Chris
Manoharan, Muthiah
Swirski, Filip K
Weissleder, Ralph
Langer, Robert
Anderson, Daniel G
de Fougerolles, Antonin
Nahrendorf, Matthias
Koteliansky, Victor
author_facet Novobrantseva, Tatiana I
Borodovsky, Anna
Wong, Jamie
Klebanov, Boris
Zafari, Mohammad
Yucius, Kristina
Querbes, William
Ge, Pei
Ruda, Vera M
Milstein, Stuart
Speciner, Lauren
Duncan, Rick
Barros, Scott
Basha, Genc
Cullis, Pieter
Akinc, Akin
Donahoe, Jessica S
Narayanannair Jayaprakash, K
Jayaraman, Muthusamy
Bogorad, Roman L
Love, Kevin
Whitehead, Katie
Levins, Chris
Manoharan, Muthiah
Swirski, Filip K
Weissleder, Ralph
Langer, Robert
Anderson, Daniel G
de Fougerolles, Antonin
Nahrendorf, Matthias
Koteliansky, Victor
author_sort Novobrantseva, Tatiana I
collection PubMed
description 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.
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spelling pubmed-33815932012-07-03 Systemic RNAi-mediated Gene Silencing in Nonhuman Primate and Rodent Myeloid Cells Novobrantseva, Tatiana I Borodovsky, Anna Wong, Jamie Klebanov, Boris Zafari, Mohammad Yucius, Kristina Querbes, William Ge, Pei Ruda, Vera M Milstein, Stuart Speciner, Lauren Duncan, Rick Barros, Scott Basha, Genc Cullis, Pieter Akinc, Akin Donahoe, Jessica S Narayanannair Jayaprakash, K Jayaraman, Muthusamy Bogorad, Roman L Love, Kevin Whitehead, Katie Levins, Chris Manoharan, Muthiah Swirski, Filip K Weissleder, Ralph Langer, Robert Anderson, Daniel G de Fougerolles, Antonin Nahrendorf, Matthias Koteliansky, Victor Mol Ther Nucleic Acids Original Article 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. Nature Publishing Group 2012-01 2012-01-24 /pmc/articles/PMC3381593/ /pubmed/23344621 http://dx.doi.org/10.1038/mtna.2011.3 Text en Copyright © 2012 American Society of Gene & Cell Therapy http://creativecommons.org/licenses/by-nc-nd/3.0/ Molecular Therapy-Nucleic Acids is an open-access journal published by Nature Publishing Group. This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Original Article
Novobrantseva, Tatiana I
Borodovsky, Anna
Wong, Jamie
Klebanov, Boris
Zafari, Mohammad
Yucius, Kristina
Querbes, William
Ge, Pei
Ruda, Vera M
Milstein, Stuart
Speciner, Lauren
Duncan, Rick
Barros, Scott
Basha, Genc
Cullis, Pieter
Akinc, Akin
Donahoe, Jessica S
Narayanannair Jayaprakash, K
Jayaraman, Muthusamy
Bogorad, Roman L
Love, Kevin
Whitehead, Katie
Levins, Chris
Manoharan, Muthiah
Swirski, Filip K
Weissleder, Ralph
Langer, Robert
Anderson, Daniel G
de Fougerolles, Antonin
Nahrendorf, Matthias
Koteliansky, Victor
Systemic RNAi-mediated Gene Silencing in Nonhuman Primate and Rodent Myeloid Cells
title Systemic RNAi-mediated Gene Silencing in Nonhuman Primate and Rodent Myeloid Cells
title_full Systemic RNAi-mediated Gene Silencing in Nonhuman Primate and Rodent Myeloid Cells
title_fullStr Systemic RNAi-mediated Gene Silencing in Nonhuman Primate and Rodent Myeloid Cells
title_full_unstemmed Systemic RNAi-mediated Gene Silencing in Nonhuman Primate and Rodent Myeloid Cells
title_short Systemic RNAi-mediated Gene Silencing in Nonhuman Primate and Rodent Myeloid Cells
title_sort systemic rnai-mediated gene silencing in nonhuman primate and rodent myeloid cells
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3381593/
https://www.ncbi.nlm.nih.gov/pubmed/23344621
http://dx.doi.org/10.1038/mtna.2011.3
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