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Placental Homing Peptide-microRNA Inhibitor Conjugates for Targeted Enhancement of Intrinsic Placental Growth Signaling
Suboptimal placental growth and development are the underlying cause of many pregnancy complications. No treatments are available, primarily due to the risk of causing fetal teratogenicity. microRNAs (miRNAs) are short, non-coding RNA sequences that regulate multiple downstream genes; miR-145 and mi...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562227/ https://www.ncbi.nlm.nih.gov/pubmed/28824727 http://dx.doi.org/10.7150/thno.18845 |
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author | Beards, Frances Jones, Lisa E Charnock, Jayne Forbes, Karen Harris, Lynda K |
author_facet | Beards, Frances Jones, Lisa E Charnock, Jayne Forbes, Karen Harris, Lynda K |
author_sort | Beards, Frances |
collection | PubMed |
description | Suboptimal placental growth and development are the underlying cause of many pregnancy complications. No treatments are available, primarily due to the risk of causing fetal teratogenicity. microRNAs (miRNAs) are short, non-coding RNA sequences that regulate multiple downstream genes; miR-145 and miR675 have previously been identified as negative regulators of placental growth. In this proof of principle study, we explored the feasibility of delivering miRNA inhibitors to the placentas of pregnant mice and developed novel placental homing peptide-microRNA inhibitor conjugates for targeted enhancement of intrinsic placental growth signalling. Scrambled-, miR-145- or miR-675 inhibitor sequences were synthesised from peptide nucleic acids and conjugated to the placental homing peptide CCGKRK. Intravenous administration of the miR-145- and miR-675 conjugates to pregnant C57BL/6J mice significantly increased fetal and placental weights compared to controls; the miR-675 conjugate significantly reduced placental miR-675 expression. When applied to human first trimester placental explants, the miR-145 conjugate significantly reduced placental miR-145 expression, and both conjugates induced significant enhancement of cytotrophoblast proliferation; no effect was observed in term placental explants. This study demonstrates that homing peptide-miRNA inhibitor conjugates can be exploited to promote placental growth; these novel therapeutics may represent an innovative strategy for targeted treatment of compromised placental development. |
format | Online Article Text |
id | pubmed-5562227 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-55622272017-08-18 Placental Homing Peptide-microRNA Inhibitor Conjugates for Targeted Enhancement of Intrinsic Placental Growth Signaling Beards, Frances Jones, Lisa E Charnock, Jayne Forbes, Karen Harris, Lynda K Theranostics Research Paper Suboptimal placental growth and development are the underlying cause of many pregnancy complications. No treatments are available, primarily due to the risk of causing fetal teratogenicity. microRNAs (miRNAs) are short, non-coding RNA sequences that regulate multiple downstream genes; miR-145 and miR675 have previously been identified as negative regulators of placental growth. In this proof of principle study, we explored the feasibility of delivering miRNA inhibitors to the placentas of pregnant mice and developed novel placental homing peptide-microRNA inhibitor conjugates for targeted enhancement of intrinsic placental growth signalling. Scrambled-, miR-145- or miR-675 inhibitor sequences were synthesised from peptide nucleic acids and conjugated to the placental homing peptide CCGKRK. Intravenous administration of the miR-145- and miR-675 conjugates to pregnant C57BL/6J mice significantly increased fetal and placental weights compared to controls; the miR-675 conjugate significantly reduced placental miR-675 expression. When applied to human first trimester placental explants, the miR-145 conjugate significantly reduced placental miR-145 expression, and both conjugates induced significant enhancement of cytotrophoblast proliferation; no effect was observed in term placental explants. This study demonstrates that homing peptide-miRNA inhibitor conjugates can be exploited to promote placental growth; these novel therapeutics may represent an innovative strategy for targeted treatment of compromised placental development. Ivyspring International Publisher 2017-07-14 /pmc/articles/PMC5562227/ /pubmed/28824727 http://dx.doi.org/10.7150/thno.18845 Text en © The authors This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Beards, Frances Jones, Lisa E Charnock, Jayne Forbes, Karen Harris, Lynda K Placental Homing Peptide-microRNA Inhibitor Conjugates for Targeted Enhancement of Intrinsic Placental Growth Signaling |
title | Placental Homing Peptide-microRNA Inhibitor Conjugates for Targeted Enhancement of Intrinsic Placental Growth Signaling |
title_full | Placental Homing Peptide-microRNA Inhibitor Conjugates for Targeted Enhancement of Intrinsic Placental Growth Signaling |
title_fullStr | Placental Homing Peptide-microRNA Inhibitor Conjugates for Targeted Enhancement of Intrinsic Placental Growth Signaling |
title_full_unstemmed | Placental Homing Peptide-microRNA Inhibitor Conjugates for Targeted Enhancement of Intrinsic Placental Growth Signaling |
title_short | Placental Homing Peptide-microRNA Inhibitor Conjugates for Targeted Enhancement of Intrinsic Placental Growth Signaling |
title_sort | placental homing peptide-microrna inhibitor conjugates for targeted enhancement of intrinsic placental growth signaling |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562227/ https://www.ncbi.nlm.nih.gov/pubmed/28824727 http://dx.doi.org/10.7150/thno.18845 |
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