Improving mRNA-Based Therapeutic Gene Delivery by Expression-Augmenting 3' UTRs Identified by Cellular Library Screening.
3' Untranslated Regions
/ genetics
Animals
Blood Donors
Cancer Vaccines
Cells, Cultured
Cellular Reprogramming
/ genetics
Female
Fibroblasts
Gene Library
Gene Transfer Techniques
Genetic Therapy
/ methods
Half-Life
Humans
Induced Pluripotent Stem Cells
Mice
Mice, Inbred BALB C
RNA Stability
RNA, Messenger
/ genetics
Vaccination
3’ UTR library
RNA stability
cancer immunotherapy
cellular reprogramming
iPSCs
mRNA pharmacokinetics
mRNA therapeutics
Journal
Molecular therapy : the journal of the American Society of Gene Therapy
ISSN: 1525-0024
Titre abrégé: Mol Ther
Pays: United States
ID NLM: 100890581
Informations de publication
Date de publication:
10 04 2019
10 04 2019
Historique:
received:
27
09
2018
revised:
11
12
2018
accepted:
11
12
2018
pubmed:
15
1
2019
medline:
9
4
2020
entrez:
15
1
2019
Statut:
ppublish
Résumé
Synthetic mRNA has emerged as a powerful tool for the transfer of genetic information, and it is being explored for a variety of therapeutic applications. Many of these applications require prolonged intracellular persistence of mRNA to improve bioavailability of the encoded protein. mRNA molecules are intrinsically unstable and their intracellular kinetics depend on the UTRs embracing the coding sequence, in particular the 3' UTR elements. We describe here a novel and generally applicable cell-based selection process for the identification of 3' UTRs that augment the expression of proteins encoded by synthetic mRNA. Moreover, we show, for two applications of mRNA therapeutics, namely, (1) the delivery of vaccine antigens in order to mount T cell immune responses and (2) the introduction of reprogramming factors into differentiated cells in order to induce pluripotency, that mRNAs tagged with the 3' UTR elements discovered in this study outperform those with commonly used 3' UTRs. This approach further leverages the utility of mRNA as a gene therapy drug format.
Identifiants
pubmed: 30638957
pii: S1525-0016(18)30595-1
doi: 10.1016/j.ymthe.2018.12.011
pmc: PMC6453560
pii:
doi:
Substances chimiques
3' Untranslated Regions
0
Cancer Vaccines
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
824-836Informations de copyright
Copyright © 2018. Published by Elsevier Inc.
Références
Nature. 2007 Jul 19;448(7151):313-7
pubmed: 17554338
Br Med Bull. 2013;106:135-59
pubmed: 23704099
J Biol Chem. 1998 Dec 25;273(52):34970-5
pubmed: 9857028
Hum Gene Ther. 2015 Nov;26(11):751-66
pubmed: 26381596
Gene Ther. 2014 May;21(5):533-8
pubmed: 24694535
Mol Ther. 2005 Oct;12(4):734-43
pubmed: 15921959
Nature. 1990 Aug 30;346(6287):818-22
pubmed: 1697402
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Stem Cells. 2017 Jan;35(1):68-79
pubmed: 27250673
Cell. 2007 Nov 30;131(5):861-72
pubmed: 18035408
Haematologica. 2011 Jun;96(6):905-13
pubmed: 21357703
Cancer Cell. 2011 Jan 18;19(1):125-37
pubmed: 21251616
Nat Rev Cancer. 2011 Apr;11(4):268-77
pubmed: 21390058
Nat Rev Genet. 2012 Dec;13(12):878-90
pubmed: 23154810
Immunity. 2000 Oct;13(4):529-38
pubmed: 11070171
Prog Nucleic Acid Res Mol Biol. 1997;57:249-87
pubmed: 9175436
Nature. 2016 Jun 01;534(7607):396-401
pubmed: 27281205
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W119-23
pubmed: 24838564
Nature. 2017 Jul 13;547(7662):222-226
pubmed: 28678784
Cell. 1976 Aug;8(4):495-503
pubmed: 954102
Gene Ther. 2010 Aug;17(8):961-71
pubmed: 20410931
Cancer Immunol Res. 2013 Dec;1(6):386-92
pubmed: 24778131
Cell Stem Cell. 2013 Aug 1;13(2):246-54
pubmed: 23910086
RNA. 2001 Mar;7(3):435-44
pubmed: 11333023
Nat Rev Drug Discov. 2014 Oct;13(10):759-80
pubmed: 25233993
Cancer Res. 2011 Oct 1;71(19):6132-42
pubmed: 21816907
J Virol. 1992 Apr;66(4):1943-50
pubmed: 1347793
Science. 1990 Aug 3;249(4968):505-10
pubmed: 2200121
Blood. 1985 Nov;66(5):1149-54
pubmed: 4052630
Wiley Interdiscip Rev RNA. 2015 Sep-Oct;6(5):471-99
pubmed: 26061157
Mol Biol Evol. 1997 May;14(5):592-3
pubmed: 9159937
Bioessays. 2014 Jun;36(6):617-26
pubmed: 24737341
Genome Res. 2003 Aug;13(8):1863-72
pubmed: 12902380
Immunity. 2003 Mar;18(3):343-54
pubmed: 12648452
Curr Opin Immunol. 2010 Feb;22(1):41-7
pubmed: 20061127
Cancer Sci. 2017 Apr;108(4):744-752
pubmed: 28178391
Gene Ther. 2011 Jul;18(7):702-8
pubmed: 21368901
Blood. 2009 Jul 9;114(2):404-14
pubmed: 19398721
Nat Rev Drug Discov. 2018 Apr;17(4):261-279
pubmed: 29326426
Cell Stem Cell. 2008 Feb 7;2(2):151-9
pubmed: 18371436
PLoS One. 2017 Jul 27;12(7):e0182018
pubmed: 28750082
Cancer Immunol Immunother. 2007 Oct;56(10):1577-87
pubmed: 17361438
Cell. 2007 Jun 29;129(7):1401-14
pubmed: 17604727
Blood. 2006 Dec 15;108(13):4009-17
pubmed: 16940422
RNA. 2008 Jun;14(6):1119-31
pubmed: 18430890
Mol Ther. 2012 May;20(5):1063-74
pubmed: 22371843
Nucleic Acid Ther. 2011 Aug;21(4):253-63
pubmed: 21793789
PLoS One. 2012;7(7):e40849
pubmed: 22808276
Cell Stem Cell. 2010 Nov 5;7(5):618-30
pubmed: 20888316
Mol Cell Biol. 1998 Dec;18(12):7304-16
pubmed: 9819417
Exp Biol Med (Maywood). 2003 Apr;228(4):387-95
pubmed: 12671183
Nature. 2011 May 19;473(7347):337-42
pubmed: 21593866
Virology. 2014 Feb;450-451:13-23
pubmed: 24503063
PLoS One. 2013 Jul 01;8(7):e67694
pubmed: 23840876
Cell Stem Cell. 2011 Apr 8;8(4):376-88
pubmed: 21474102
Gene. 2001 Mar 7;265(1-2):11-23
pubmed: 11255003
Nat Rev Mol Cell Biol. 2010 Feb;11(2):113-27
pubmed: 20094052
Mol Cell Biol. 1996 Jan;16(1):146-56
pubmed: 8524291
RNA Biol. 2011 Jan-Feb;8(1):35-43
pubmed: 21289486
Cell. 1995 May 19;81(4):551-60
pubmed: 7758109