Messenger RNA therapy for rare genetic metabolic diseases

Decades of intense research in molecular biology and biochemistry are fructifying in the emergence of therapeutic messenger RNAs (mRNA) as a new class of drugs. Synthetic mRNAs can be sequence optimised to improve translatability into proteins, as well as chemically modified to reduce immunogenicity...

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Authors: Berraondo-López, P. (Pedro)|||/items/b1f8ccc3-8e08-4ece-967c-64ccfc0e5b91, Martini, P. (Paolo)|||/items/9c6d38eb-51a3-48cd-a339-45ca9984c7e4, Avila, M.A. (Matías Antonio)|||/items/3ad9abbb-c18d-445b-86cf-cb76be15419f, Fontanellas-Romá, A. (Antonio)|||/items/4ca7871d-480e-4841-b383-6a0da85f3a81
Format: article
Publication Date:2019
Country:España
Institution:Universidad de Navarra
Repository:Dadun. Depósito Académico Digital de la Universidad de Navarra
Language:English
OAI Identifier:oai:dadun.unav.edu:10171/68667
Online Access:https://hdl.handle.net/10171/68667
Access Level:Open access
Keyword:Synthetic mRNAs
Messenger RNAs (mRNA)
Metabolic diseases
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spelling Messenger RNA therapy for rare genetic metabolic diseasesBerraondo-López, P. (Pedro)|||/items/b1f8ccc3-8e08-4ece-967c-64ccfc0e5b91Martini, P. (Paolo)|||/items/9c6d38eb-51a3-48cd-a339-45ca9984c7e4Avila, M.A. (Matías Antonio)|||/items/3ad9abbb-c18d-445b-86cf-cb76be15419fFontanellas-Romá, A. (Antonio)|||/items/4ca7871d-480e-4841-b383-6a0da85f3a81Synthetic mRNAsMessenger RNAs (mRNA)Metabolic diseasesDecades of intense research in molecular biology and biochemistry are fructifying in the emergence of therapeutic messenger RNAs (mRNA) as a new class of drugs. Synthetic mRNAs can be sequence optimised to improve translatability into proteins, as well as chemically modified to reduce immunogenicity and increase chemical stability using naturally occurring uridine modifications. These structural improvements, together with the development of safe and efficient vehicles that preserve mRNA integrity in circulation and allow targeted intracellular delivery, have paved the way for mRNA-based therapeutics. Indeed, mRNAs formulated into biodegradable lipid nanoparticles are currently being tested in preclinical and clinical studies for multiple diseases including cancer immunotherapy and vaccination for infectious diseases. An emerging application of mRNAs is the supplementation of proteins that are not expressed or are not functional in a regulated and tissue-specific manner. This so-called ‘protein replacement therapy’ could represent a solution for genetic metabolic diseases currently lacking effective treatments. Here we summarise this new class of drugs and discuss the preclinical evidence supporting the potential of liver-mediated mRNA therapy for three rare genetic conditions: methylmalonic acidaemia, acute intermittent porphyria and ornithine transcarbamylase deficiency.Dadun. Depósito Académico Digital Universidad de Navarra20242024-01-3120192019-01-0120192019-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/68667reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/686672026-06-21T12:47:57Z
dc.title.none.fl_str_mv Messenger RNA therapy for rare genetic metabolic diseases
title Messenger RNA therapy for rare genetic metabolic diseases
spellingShingle Messenger RNA therapy for rare genetic metabolic diseases
Berraondo-López, P. (Pedro)|||/items/b1f8ccc3-8e08-4ece-967c-64ccfc0e5b91
Synthetic mRNAs
Messenger RNAs (mRNA)
Metabolic diseases
title_short Messenger RNA therapy for rare genetic metabolic diseases
title_full Messenger RNA therapy for rare genetic metabolic diseases
title_fullStr Messenger RNA therapy for rare genetic metabolic diseases
title_full_unstemmed Messenger RNA therapy for rare genetic metabolic diseases
title_sort Messenger RNA therapy for rare genetic metabolic diseases
dc.creator.none.fl_str_mv Berraondo-López, P. (Pedro)|||/items/b1f8ccc3-8e08-4ece-967c-64ccfc0e5b91
Martini, P. (Paolo)|||/items/9c6d38eb-51a3-48cd-a339-45ca9984c7e4
Avila, M.A. (Matías Antonio)|||/items/3ad9abbb-c18d-445b-86cf-cb76be15419f
Fontanellas-Romá, A. (Antonio)|||/items/4ca7871d-480e-4841-b383-6a0da85f3a81
author Berraondo-López, P. (Pedro)|||/items/b1f8ccc3-8e08-4ece-967c-64ccfc0e5b91
author_facet Berraondo-López, P. (Pedro)|||/items/b1f8ccc3-8e08-4ece-967c-64ccfc0e5b91
Martini, P. (Paolo)|||/items/9c6d38eb-51a3-48cd-a339-45ca9984c7e4
Avila, M.A. (Matías Antonio)|||/items/3ad9abbb-c18d-445b-86cf-cb76be15419f
Fontanellas-Romá, A. (Antonio)|||/items/4ca7871d-480e-4841-b383-6a0da85f3a81
author_role author
author2 Martini, P. (Paolo)|||/items/9c6d38eb-51a3-48cd-a339-45ca9984c7e4
Avila, M.A. (Matías Antonio)|||/items/3ad9abbb-c18d-445b-86cf-cb76be15419f
Fontanellas-Romá, A. (Antonio)|||/items/4ca7871d-480e-4841-b383-6a0da85f3a81
author2_role author
author
author
dc.contributor.none.fl_str_mv Dadun. Depósito Académico Digital Universidad de Navarra
dc.subject.none.fl_str_mv Synthetic mRNAs
Messenger RNAs (mRNA)
Metabolic diseases
topic Synthetic mRNAs
Messenger RNAs (mRNA)
Metabolic diseases
description Decades of intense research in molecular biology and biochemistry are fructifying in the emergence of therapeutic messenger RNAs (mRNA) as a new class of drugs. Synthetic mRNAs can be sequence optimised to improve translatability into proteins, as well as chemically modified to reduce immunogenicity and increase chemical stability using naturally occurring uridine modifications. These structural improvements, together with the development of safe and efficient vehicles that preserve mRNA integrity in circulation and allow targeted intracellular delivery, have paved the way for mRNA-based therapeutics. Indeed, mRNAs formulated into biodegradable lipid nanoparticles are currently being tested in preclinical and clinical studies for multiple diseases including cancer immunotherapy and vaccination for infectious diseases. An emerging application of mRNAs is the supplementation of proteins that are not expressed or are not functional in a regulated and tissue-specific manner. This so-called ‘protein replacement therapy’ could represent a solution for genetic metabolic diseases currently lacking effective treatments. Here we summarise this new class of drugs and discuss the preclinical evidence supporting the potential of liver-mediated mRNA therapy for three rare genetic conditions: methylmalonic acidaemia, acute intermittent porphyria and ornithine transcarbamylase deficiency.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-01-01
2019
2019-01-01
2024
2024-01-31
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10171/68667
url https://hdl.handle.net/10171/68667
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra
instname:Universidad de Navarra
instname_str Universidad de Navarra
reponame_str Dadun. Depósito Académico Digital de la Universidad de Navarra
collection Dadun. Depósito Académico Digital de la Universidad de Navarra
repository.name.fl_str_mv
repository.mail.fl_str_mv
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