Cargando…
Improved in-vivo airway gene transfer via magnetic-guidance, with protocol development informed by synchrotron imaging
Gene vectors to treat cystic fibrosis lung disease should be targeted to the conducting airways, as peripheral lung transduction does not offer therapeutic benefit. Viral transduction efficiency is directly related to the vector residence time. However, delivered fluids such as gene vectors naturall...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9151774/ https://www.ncbi.nlm.nih.gov/pubmed/35637239 http://dx.doi.org/10.1038/s41598-022-12895-x |
_version_ | 1784717541784944640 |
---|---|
author | Donnelley, Martin Cmielewski, Patricia Morgan, Kaye Delhove, Juliette Reyne, Nicole McCarron, Alexandra Rout-Pitt, Nathan Drysdale, Victoria Carpentieri, Chantelle Spiers, Kathryn Takeuchi, Akihisa Uesugi, Kentaro Yagi, Naoto Parsons, David |
author_facet | Donnelley, Martin Cmielewski, Patricia Morgan, Kaye Delhove, Juliette Reyne, Nicole McCarron, Alexandra Rout-Pitt, Nathan Drysdale, Victoria Carpentieri, Chantelle Spiers, Kathryn Takeuchi, Akihisa Uesugi, Kentaro Yagi, Naoto Parsons, David |
author_sort | Donnelley, Martin |
collection | PubMed |
description | Gene vectors to treat cystic fibrosis lung disease should be targeted to the conducting airways, as peripheral lung transduction does not offer therapeutic benefit. Viral transduction efficiency is directly related to the vector residence time. However, delivered fluids such as gene vectors naturally spread to the alveoli during inspiration, and therapeutic particles of any form are rapidly cleared via mucociliary transit. Extending gene vector residence time within the conducting airways is important, but hard to achieve. Gene vector conjugated magnetic particles that can be guided to the conducting airway surfaces could improve regional targeting. Due to the challenges of in-vivo visualisation, the behaviour of such small magnetic particles on the airway surface in the presence of an applied magnetic field is poorly understood. The aim of this study was to use synchrotron imaging to visualise the in-vivo motion of a range of magnetic particles in the trachea of anaesthetised rats to examine the dynamics and patterns of individual and bulk particle behaviour in-vivo. We also then assessed whether lentiviral-magnetic particle delivery in the presence of a magnetic field increases transduction efficiency in the rat trachea. Synchrotron X-ray imaging revealed the behaviour of magnetic particles in stationary and moving magnetic fields, both in-vitro and in-vivo. Particles could not easily be dragged along the live airway surface with the magnet, but during delivery deposition was focussed within the field of view where the magnetic field was the strongest. Transduction efficiency was also improved six-fold when the lentiviral-magnetic particles were delivered in the presence of a magnetic field. Together these results show that lentiviral-magnetic particles and magnetic fields may be a valuable approach for improving gene vector targeting and increasing transduction levels in the conducting airways in-vivo. |
format | Online Article Text |
id | pubmed-9151774 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-91517742022-06-01 Improved in-vivo airway gene transfer via magnetic-guidance, with protocol development informed by synchrotron imaging Donnelley, Martin Cmielewski, Patricia Morgan, Kaye Delhove, Juliette Reyne, Nicole McCarron, Alexandra Rout-Pitt, Nathan Drysdale, Victoria Carpentieri, Chantelle Spiers, Kathryn Takeuchi, Akihisa Uesugi, Kentaro Yagi, Naoto Parsons, David Sci Rep Article Gene vectors to treat cystic fibrosis lung disease should be targeted to the conducting airways, as peripheral lung transduction does not offer therapeutic benefit. Viral transduction efficiency is directly related to the vector residence time. However, delivered fluids such as gene vectors naturally spread to the alveoli during inspiration, and therapeutic particles of any form are rapidly cleared via mucociliary transit. Extending gene vector residence time within the conducting airways is important, but hard to achieve. Gene vector conjugated magnetic particles that can be guided to the conducting airway surfaces could improve regional targeting. Due to the challenges of in-vivo visualisation, the behaviour of such small magnetic particles on the airway surface in the presence of an applied magnetic field is poorly understood. The aim of this study was to use synchrotron imaging to visualise the in-vivo motion of a range of magnetic particles in the trachea of anaesthetised rats to examine the dynamics and patterns of individual and bulk particle behaviour in-vivo. We also then assessed whether lentiviral-magnetic particle delivery in the presence of a magnetic field increases transduction efficiency in the rat trachea. Synchrotron X-ray imaging revealed the behaviour of magnetic particles in stationary and moving magnetic fields, both in-vitro and in-vivo. Particles could not easily be dragged along the live airway surface with the magnet, but during delivery deposition was focussed within the field of view where the magnetic field was the strongest. Transduction efficiency was also improved six-fold when the lentiviral-magnetic particles were delivered in the presence of a magnetic field. Together these results show that lentiviral-magnetic particles and magnetic fields may be a valuable approach for improving gene vector targeting and increasing transduction levels in the conducting airways in-vivo. Nature Publishing Group UK 2022-05-30 /pmc/articles/PMC9151774/ /pubmed/35637239 http://dx.doi.org/10.1038/s41598-022-12895-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Donnelley, Martin Cmielewski, Patricia Morgan, Kaye Delhove, Juliette Reyne, Nicole McCarron, Alexandra Rout-Pitt, Nathan Drysdale, Victoria Carpentieri, Chantelle Spiers, Kathryn Takeuchi, Akihisa Uesugi, Kentaro Yagi, Naoto Parsons, David Improved in-vivo airway gene transfer via magnetic-guidance, with protocol development informed by synchrotron imaging |
title | Improved in-vivo airway gene transfer via magnetic-guidance, with protocol development informed by synchrotron imaging |
title_full | Improved in-vivo airway gene transfer via magnetic-guidance, with protocol development informed by synchrotron imaging |
title_fullStr | Improved in-vivo airway gene transfer via magnetic-guidance, with protocol development informed by synchrotron imaging |
title_full_unstemmed | Improved in-vivo airway gene transfer via magnetic-guidance, with protocol development informed by synchrotron imaging |
title_short | Improved in-vivo airway gene transfer via magnetic-guidance, with protocol development informed by synchrotron imaging |
title_sort | improved in-vivo airway gene transfer via magnetic-guidance, with protocol development informed by synchrotron imaging |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9151774/ https://www.ncbi.nlm.nih.gov/pubmed/35637239 http://dx.doi.org/10.1038/s41598-022-12895-x |
work_keys_str_mv | AT donnelleymartin improvedinvivoairwaygenetransferviamagneticguidancewithprotocoldevelopmentinformedbysynchrotronimaging AT cmielewskipatricia improvedinvivoairwaygenetransferviamagneticguidancewithprotocoldevelopmentinformedbysynchrotronimaging AT morgankaye improvedinvivoairwaygenetransferviamagneticguidancewithprotocoldevelopmentinformedbysynchrotronimaging AT delhovejuliette improvedinvivoairwaygenetransferviamagneticguidancewithprotocoldevelopmentinformedbysynchrotronimaging AT reynenicole improvedinvivoairwaygenetransferviamagneticguidancewithprotocoldevelopmentinformedbysynchrotronimaging AT mccarronalexandra improvedinvivoairwaygenetransferviamagneticguidancewithprotocoldevelopmentinformedbysynchrotronimaging AT routpittnathan improvedinvivoairwaygenetransferviamagneticguidancewithprotocoldevelopmentinformedbysynchrotronimaging AT drysdalevictoria improvedinvivoairwaygenetransferviamagneticguidancewithprotocoldevelopmentinformedbysynchrotronimaging AT carpentierichantelle improvedinvivoairwaygenetransferviamagneticguidancewithprotocoldevelopmentinformedbysynchrotronimaging AT spierskathryn improvedinvivoairwaygenetransferviamagneticguidancewithprotocoldevelopmentinformedbysynchrotronimaging AT takeuchiakihisa improvedinvivoairwaygenetransferviamagneticguidancewithprotocoldevelopmentinformedbysynchrotronimaging AT uesugikentaro improvedinvivoairwaygenetransferviamagneticguidancewithprotocoldevelopmentinformedbysynchrotronimaging AT yaginaoto improvedinvivoairwaygenetransferviamagneticguidancewithprotocoldevelopmentinformedbysynchrotronimaging AT parsonsdavid improvedinvivoairwaygenetransferviamagneticguidancewithprotocoldevelopmentinformedbysynchrotronimaging |