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Characterization of BNT162b2 mRNA to Evaluate Risk of Off-Target Antigen Translation

mRNA vaccines have been established as a safe and effective modality, thanks in large part to the expedited development and approval of COVID-19 vaccines. In addition to the active, full-length mRNA transcript, mRNA fragment species can be present as a byproduct of the cell-free transcription manufa...

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Autores principales: Patel, Himakshi K., Zhang, Kun, Utegg, Rachael, Stephens, Elaine, Salem, Shauna, Welch, Heidi, Grobe, Svenja, Schlereth, Julia, Kuhn, Andreas N., Ryczek, Jeff, Cirelli, David J., Lerch, Thomas F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Authors. Published by Elsevier Inc. on behalf of American Pharmacists Association. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9836996/
https://www.ncbi.nlm.nih.gov/pubmed/36642376
http://dx.doi.org/10.1016/j.xphs.2023.01.007
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author Patel, Himakshi K.
Zhang, Kun
Utegg, Rachael
Stephens, Elaine
Salem, Shauna
Welch, Heidi
Grobe, Svenja
Schlereth, Julia
Kuhn, Andreas N.
Ryczek, Jeff
Cirelli, David J.
Lerch, Thomas F.
author_facet Patel, Himakshi K.
Zhang, Kun
Utegg, Rachael
Stephens, Elaine
Salem, Shauna
Welch, Heidi
Grobe, Svenja
Schlereth, Julia
Kuhn, Andreas N.
Ryczek, Jeff
Cirelli, David J.
Lerch, Thomas F.
author_sort Patel, Himakshi K.
collection PubMed
description mRNA vaccines have been established as a safe and effective modality, thanks in large part to the expedited development and approval of COVID-19 vaccines. In addition to the active, full-length mRNA transcript, mRNA fragment species can be present as a byproduct of the cell-free transcription manufacturing process or due to mRNA hydrolysis. In the current study, mRNA fragment species from BNT162b2 mRNA were isolated and characterized. The translational viability of intact and fragmented mRNA species was further explored using orthogonal expression systems to understand the risk of truncated spike protein or off-target antigen translation. The study demonstrates that mRNA fragments are primarily derived from premature transcriptional termination during manufacturing, and only full-length mRNA transcripts are viable for expression of the SARS-CoV-2 spike protein antigen.
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spelling pubmed-98369962023-01-17 Characterization of BNT162b2 mRNA to Evaluate Risk of Off-Target Antigen Translation Patel, Himakshi K. Zhang, Kun Utegg, Rachael Stephens, Elaine Salem, Shauna Welch, Heidi Grobe, Svenja Schlereth, Julia Kuhn, Andreas N. Ryczek, Jeff Cirelli, David J. Lerch, Thomas F. J Pharm Sci Pharmaceutical Biotechnology mRNA vaccines have been established as a safe and effective modality, thanks in large part to the expedited development and approval of COVID-19 vaccines. In addition to the active, full-length mRNA transcript, mRNA fragment species can be present as a byproduct of the cell-free transcription manufacturing process or due to mRNA hydrolysis. In the current study, mRNA fragment species from BNT162b2 mRNA were isolated and characterized. The translational viability of intact and fragmented mRNA species was further explored using orthogonal expression systems to understand the risk of truncated spike protein or off-target antigen translation. The study demonstrates that mRNA fragments are primarily derived from premature transcriptional termination during manufacturing, and only full-length mRNA transcripts are viable for expression of the SARS-CoV-2 spike protein antigen. The Authors. Published by Elsevier Inc. on behalf of American Pharmacists Association. 2023-05 2023-01-13 /pmc/articles/PMC9836996/ /pubmed/36642376 http://dx.doi.org/10.1016/j.xphs.2023.01.007 Text en © 2023 The Authors Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Pharmaceutical Biotechnology
Patel, Himakshi K.
Zhang, Kun
Utegg, Rachael
Stephens, Elaine
Salem, Shauna
Welch, Heidi
Grobe, Svenja
Schlereth, Julia
Kuhn, Andreas N.
Ryczek, Jeff
Cirelli, David J.
Lerch, Thomas F.
Characterization of BNT162b2 mRNA to Evaluate Risk of Off-Target Antigen Translation
title Characterization of BNT162b2 mRNA to Evaluate Risk of Off-Target Antigen Translation
title_full Characterization of BNT162b2 mRNA to Evaluate Risk of Off-Target Antigen Translation
title_fullStr Characterization of BNT162b2 mRNA to Evaluate Risk of Off-Target Antigen Translation
title_full_unstemmed Characterization of BNT162b2 mRNA to Evaluate Risk of Off-Target Antigen Translation
title_short Characterization of BNT162b2 mRNA to Evaluate Risk of Off-Target Antigen Translation
title_sort characterization of bnt162b2 mrna to evaluate risk of off-target antigen translation
topic Pharmaceutical Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9836996/
https://www.ncbi.nlm.nih.gov/pubmed/36642376
http://dx.doi.org/10.1016/j.xphs.2023.01.007
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