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Understanding Intracellular Biology to Improve mRNA Delivery by Lipid Nanoparticles
Poor understanding of intracellular delivery and targeting hinders development of nucleic acid-based therapeutics transported by nanoparticles. Utilizing a siRNA-targeting and small molecule profiling approach with advanced imaging and machine learning biological insights is generated into the mecha...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7615154/ https://www.ncbi.nlm.nih.gov/pubmed/37317010 http://dx.doi.org/10.1002/smtd.202201695 |
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author | Hunter, Morag Rose Cui, Lili Porebski, Benjamin Thomas Pereira, Sara Sonzini, Silvia Odunze, Uchechukwu Iyer, Preeti Engkvist, Ola Lloyd, Rebecca Louise Peel, Samantha Sabirsh, Alan Ross-Thriepland, Douglas Jones, Arwyn Tomos Desai, Arpan Shailesh |
author_facet | Hunter, Morag Rose Cui, Lili Porebski, Benjamin Thomas Pereira, Sara Sonzini, Silvia Odunze, Uchechukwu Iyer, Preeti Engkvist, Ola Lloyd, Rebecca Louise Peel, Samantha Sabirsh, Alan Ross-Thriepland, Douglas Jones, Arwyn Tomos Desai, Arpan Shailesh |
author_sort | Hunter, Morag Rose |
collection | PubMed |
description | Poor understanding of intracellular delivery and targeting hinders development of nucleic acid-based therapeutics transported by nanoparticles. Utilizing a siRNA-targeting and small molecule profiling approach with advanced imaging and machine learning biological insights is generated into the mechanism of lipid nanoparticle (MC3-LNP) delivery of mRNA. This workflow is termed Advanced Cellular and Endocytic profiling for Intracellular Delivery (ACE-ID). A cell-based imaging assay and perturbation of 178 targets relevant to intracellular trafficking is used to identify corresponding effects on functional mRNA delivery. Targets improving delivery are analyzed by extracting data-rich phenotypic fingerprints from images using advanced image analysis algorithms. Machine learning is used to determine key features correlating with enhanced delivery, identifying fluid-phase endocytosis as a productive cellular entry route. With this new knowledge, MC3-LNP is re-engineered to target macropinocytosis, and this significantly improves mRNA delivery in vitro and in vivo. The ACE-ID approach can be broadly applicable for optimizing nanomedicine-based intracellular delivery systems and has the potential to accelerate the development of delivery systems for nucleic acid-based therapeutics. |
format | Online Article Text |
id | pubmed-7615154 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
record_format | MEDLINE/PubMed |
spelling | pubmed-76151542023-10-06 Understanding Intracellular Biology to Improve mRNA Delivery by Lipid Nanoparticles Hunter, Morag Rose Cui, Lili Porebski, Benjamin Thomas Pereira, Sara Sonzini, Silvia Odunze, Uchechukwu Iyer, Preeti Engkvist, Ola Lloyd, Rebecca Louise Peel, Samantha Sabirsh, Alan Ross-Thriepland, Douglas Jones, Arwyn Tomos Desai, Arpan Shailesh Small Methods Article Poor understanding of intracellular delivery and targeting hinders development of nucleic acid-based therapeutics transported by nanoparticles. Utilizing a siRNA-targeting and small molecule profiling approach with advanced imaging and machine learning biological insights is generated into the mechanism of lipid nanoparticle (MC3-LNP) delivery of mRNA. This workflow is termed Advanced Cellular and Endocytic profiling for Intracellular Delivery (ACE-ID). A cell-based imaging assay and perturbation of 178 targets relevant to intracellular trafficking is used to identify corresponding effects on functional mRNA delivery. Targets improving delivery are analyzed by extracting data-rich phenotypic fingerprints from images using advanced image analysis algorithms. Machine learning is used to determine key features correlating with enhanced delivery, identifying fluid-phase endocytosis as a productive cellular entry route. With this new knowledge, MC3-LNP is re-engineered to target macropinocytosis, and this significantly improves mRNA delivery in vitro and in vivo. The ACE-ID approach can be broadly applicable for optimizing nanomedicine-based intracellular delivery systems and has the potential to accelerate the development of delivery systems for nucleic acid-based therapeutics. 2023-09-01 2023-06-14 /pmc/articles/PMC7615154/ /pubmed/37317010 http://dx.doi.org/10.1002/smtd.202201695 Text en https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/) https://creativecommons.org/licenses/by/4.0/This work is licensed under a BY 4.0 (https://creativecommons.org/licenses/by/4.0/) International license. |
spellingShingle | Article Hunter, Morag Rose Cui, Lili Porebski, Benjamin Thomas Pereira, Sara Sonzini, Silvia Odunze, Uchechukwu Iyer, Preeti Engkvist, Ola Lloyd, Rebecca Louise Peel, Samantha Sabirsh, Alan Ross-Thriepland, Douglas Jones, Arwyn Tomos Desai, Arpan Shailesh Understanding Intracellular Biology to Improve mRNA Delivery by Lipid Nanoparticles |
title | Understanding Intracellular Biology to Improve mRNA Delivery by Lipid Nanoparticles |
title_full | Understanding Intracellular Biology to Improve mRNA Delivery by Lipid Nanoparticles |
title_fullStr | Understanding Intracellular Biology to Improve mRNA Delivery by Lipid Nanoparticles |
title_full_unstemmed | Understanding Intracellular Biology to Improve mRNA Delivery by Lipid Nanoparticles |
title_short | Understanding Intracellular Biology to Improve mRNA Delivery by Lipid Nanoparticles |
title_sort | understanding intracellular biology to improve mrna delivery by lipid nanoparticles |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7615154/ https://www.ncbi.nlm.nih.gov/pubmed/37317010 http://dx.doi.org/10.1002/smtd.202201695 |
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