mRNA vaccine quality analysis using RNA sequencing

Abstract The success of mRNA vaccines has been realised, in part, by advances in manufacturing that enabled billions of doses to be produced at sufficient quality and safety. However, mRNA vaccines must be rigorously analysed to measure their integrity and detect contaminants that reduce their effec...

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Main Authors: Helen M. Gunter, Senel Idrisoglu, Swati Singh, Dae Jong Han, Emily Ariens, Jonathan R. Peters, Ted Wong, Seth W. Cheetham, Jun Xu, Subash Kumar Rai, Robert Feldman, Andy Herbert, Esteban Marcellin, Romain Tropee, Trent Munro, Tim R. Mercer
Format: Article
Language:English
Published: Nature Portfolio 2023-09-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-023-41354-y
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author Helen M. Gunter
Senel Idrisoglu
Swati Singh
Dae Jong Han
Emily Ariens
Jonathan R. Peters
Ted Wong
Seth W. Cheetham
Jun Xu
Subash Kumar Rai
Robert Feldman
Andy Herbert
Esteban Marcellin
Romain Tropee
Trent Munro
Tim R. Mercer
author_facet Helen M. Gunter
Senel Idrisoglu
Swati Singh
Dae Jong Han
Emily Ariens
Jonathan R. Peters
Ted Wong
Seth W. Cheetham
Jun Xu
Subash Kumar Rai
Robert Feldman
Andy Herbert
Esteban Marcellin
Romain Tropee
Trent Munro
Tim R. Mercer
author_sort Helen M. Gunter
collection DOAJ
description Abstract The success of mRNA vaccines has been realised, in part, by advances in manufacturing that enabled billions of doses to be produced at sufficient quality and safety. However, mRNA vaccines must be rigorously analysed to measure their integrity and detect contaminants that reduce their effectiveness and induce side-effects. Currently, mRNA vaccines and therapies are analysed using a range of time-consuming and costly methods. Here we describe a streamlined method to analyse mRNA vaccines and therapies using long-read nanopore sequencing. Compared to other industry-standard techniques, VAX-seq can comprehensively measure key mRNA vaccine quality attributes, including sequence, length, integrity, and purity. We also show how direct RNA sequencing can analyse mRNA chemistry, including the detection of nucleoside modifications. To support this approach, we provide supporting software to automatically report on mRNA and plasmid template quality and integrity. Given these advantages, we anticipate that RNA sequencing methods, such as VAX-seq, will become central to the development and manufacture of mRNA drugs.
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spelling doaj.art-8388e058a320472e9d9b36af0a5c254f2023-11-20T10:13:29ZengNature PortfolioNature Communications2041-17232023-09-0114111210.1038/s41467-023-41354-ymRNA vaccine quality analysis using RNA sequencingHelen M. Gunter0Senel Idrisoglu1Swati Singh2Dae Jong Han3Emily Ariens4Jonathan R. Peters5Ted Wong6Seth W. Cheetham7Jun Xu8Subash Kumar Rai9Robert Feldman10Andy Herbert11Esteban Marcellin12Romain Tropee13Trent Munro14Tim R. Mercer15Australian Institute for Bioengineering and Nanotechnology, University of QueenslandAustralian Institute for Bioengineering and Nanotechnology, University of QueenslandAustralian Institute for Bioengineering and Nanotechnology, University of QueenslandBASE facility, University of QueenslandBASE facility, University of QueenslandBASE facility, University of QueenslandGarvan Institute of Medical ResearchAustralian Institute for Bioengineering and Nanotechnology, University of QueenslandGenome Innovation Hub, University of QueenslandGenome Innovation Hub, University of QueenslandCOVID19 Vaccine Corporation Limited (CVC)COVID19 Vaccine Corporation Limited (CVC)Australian Institute for Bioengineering and Nanotechnology, University of QueenslandBASE facility, University of QueenslandAustralian Institute for Bioengineering and Nanotechnology, University of QueenslandAustralian Institute for Bioengineering and Nanotechnology, University of QueenslandAbstract The success of mRNA vaccines has been realised, in part, by advances in manufacturing that enabled billions of doses to be produced at sufficient quality and safety. However, mRNA vaccines must be rigorously analysed to measure their integrity and detect contaminants that reduce their effectiveness and induce side-effects. Currently, mRNA vaccines and therapies are analysed using a range of time-consuming and costly methods. Here we describe a streamlined method to analyse mRNA vaccines and therapies using long-read nanopore sequencing. Compared to other industry-standard techniques, VAX-seq can comprehensively measure key mRNA vaccine quality attributes, including sequence, length, integrity, and purity. We also show how direct RNA sequencing can analyse mRNA chemistry, including the detection of nucleoside modifications. To support this approach, we provide supporting software to automatically report on mRNA and plasmid template quality and integrity. Given these advantages, we anticipate that RNA sequencing methods, such as VAX-seq, will become central to the development and manufacture of mRNA drugs.https://doi.org/10.1038/s41467-023-41354-y
spellingShingle Helen M. Gunter
Senel Idrisoglu
Swati Singh
Dae Jong Han
Emily Ariens
Jonathan R. Peters
Ted Wong
Seth W. Cheetham
Jun Xu
Subash Kumar Rai
Robert Feldman
Andy Herbert
Esteban Marcellin
Romain Tropee
Trent Munro
Tim R. Mercer
mRNA vaccine quality analysis using RNA sequencing
Nature Communications
title mRNA vaccine quality analysis using RNA sequencing
title_full mRNA vaccine quality analysis using RNA sequencing
title_fullStr mRNA vaccine quality analysis using RNA sequencing
title_full_unstemmed mRNA vaccine quality analysis using RNA sequencing
title_short mRNA vaccine quality analysis using RNA sequencing
title_sort mrna vaccine quality analysis using rna sequencing
url https://doi.org/10.1038/s41467-023-41354-y
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