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Gene Therapy for Neuropathic Pain through siRNA-IRF5 Gene Delivery with Homing Peptides to Microglia

Astrocyte- and microglia-targeting peptides were identified and isolated using phage display technology. A series of procedures, including three cycles of both in vivo and in vitro biopanning, was performed separately in astrocytes and in M1 or M2 microglia, yielding 50–58 phage plaques in each cell...

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Autores principales: Terashima, Tomoya, Ogawa, Nobuhiro, Nakae, Yuki, Sato, Toshiyuki, Katagi, Miwako, Okano, Junko, Maegawa, Hiroshi, Kojima, Hideto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5992689/
https://www.ncbi.nlm.nih.gov/pubmed/29858055
http://dx.doi.org/10.1016/j.omtn.2018.02.007
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author Terashima, Tomoya
Ogawa, Nobuhiro
Nakae, Yuki
Sato, Toshiyuki
Katagi, Miwako
Okano, Junko
Maegawa, Hiroshi
Kojima, Hideto
author_facet Terashima, Tomoya
Ogawa, Nobuhiro
Nakae, Yuki
Sato, Toshiyuki
Katagi, Miwako
Okano, Junko
Maegawa, Hiroshi
Kojima, Hideto
author_sort Terashima, Tomoya
collection PubMed
description Astrocyte- and microglia-targeting peptides were identified and isolated using phage display technology. A series of procedures, including three cycles of both in vivo and in vitro biopanning, was performed separately in astrocytes and in M1 or M2 microglia, yielding 50–58 phage plaques in each cell type. Analyses of the sequences of this collection identified one candidate homing peptide targeting astrocytes (AS1[C-LNSSQPS-C]) and two candidate homing peptides targeting microglia (MG1[C-HHSSSAR-C] and MG2[C-NTGSPYE-C]). To determine peptide specificity for the target cell in vitro, each peptide was synthesized and introduced into the primary cultures of astrocytes or microglia. Those peptides could bind to the target cells and be selectively taken up by the corresponding cell, namely, astrocytes, M1 microglia, or M2 microglia. To confirm cell-specific gene delivery to M1 microglia, the complexes between peptide MG1 and siRNA-interferon regulatory factor 5 were prepared and intrathecally injected into a mouse model of neuropathic pain. The complexes successfully suppressed hyperalgesia with high efficiency in this neuropathic pain model. Here, we describe a novel gene therapy for the treatment neuropathic pain, which has a high potential to be of clinical relevance. This strategy will ensure the targeted delivery of therapeutic genes while minimizing side effects to non-target tissues or cells.
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spelling pubmed-59926892018-07-19 Gene Therapy for Neuropathic Pain through siRNA-IRF5 Gene Delivery with Homing Peptides to Microglia Terashima, Tomoya Ogawa, Nobuhiro Nakae, Yuki Sato, Toshiyuki Katagi, Miwako Okano, Junko Maegawa, Hiroshi Kojima, Hideto Mol Ther Nucleic Acids Article Astrocyte- and microglia-targeting peptides were identified and isolated using phage display technology. A series of procedures, including three cycles of both in vivo and in vitro biopanning, was performed separately in astrocytes and in M1 or M2 microglia, yielding 50–58 phage plaques in each cell type. Analyses of the sequences of this collection identified one candidate homing peptide targeting astrocytes (AS1[C-LNSSQPS-C]) and two candidate homing peptides targeting microglia (MG1[C-HHSSSAR-C] and MG2[C-NTGSPYE-C]). To determine peptide specificity for the target cell in vitro, each peptide was synthesized and introduced into the primary cultures of astrocytes or microglia. Those peptides could bind to the target cells and be selectively taken up by the corresponding cell, namely, astrocytes, M1 microglia, or M2 microglia. To confirm cell-specific gene delivery to M1 microglia, the complexes between peptide MG1 and siRNA-interferon regulatory factor 5 were prepared and intrathecally injected into a mouse model of neuropathic pain. The complexes successfully suppressed hyperalgesia with high efficiency in this neuropathic pain model. Here, we describe a novel gene therapy for the treatment neuropathic pain, which has a high potential to be of clinical relevance. This strategy will ensure the targeted delivery of therapeutic genes while minimizing side effects to non-target tissues or cells. American Society of Gene & Cell Therapy 2018-02-27 /pmc/articles/PMC5992689/ /pubmed/29858055 http://dx.doi.org/10.1016/j.omtn.2018.02.007 Text en © 2018 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Terashima, Tomoya
Ogawa, Nobuhiro
Nakae, Yuki
Sato, Toshiyuki
Katagi, Miwako
Okano, Junko
Maegawa, Hiroshi
Kojima, Hideto
Gene Therapy for Neuropathic Pain through siRNA-IRF5 Gene Delivery with Homing Peptides to Microglia
title Gene Therapy for Neuropathic Pain through siRNA-IRF5 Gene Delivery with Homing Peptides to Microglia
title_full Gene Therapy for Neuropathic Pain through siRNA-IRF5 Gene Delivery with Homing Peptides to Microglia
title_fullStr Gene Therapy for Neuropathic Pain through siRNA-IRF5 Gene Delivery with Homing Peptides to Microglia
title_full_unstemmed Gene Therapy for Neuropathic Pain through siRNA-IRF5 Gene Delivery with Homing Peptides to Microglia
title_short Gene Therapy for Neuropathic Pain through siRNA-IRF5 Gene Delivery with Homing Peptides to Microglia
title_sort gene therapy for neuropathic pain through sirna-irf5 gene delivery with homing peptides to microglia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5992689/
https://www.ncbi.nlm.nih.gov/pubmed/29858055
http://dx.doi.org/10.1016/j.omtn.2018.02.007
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