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Modified mRNA as an alternative to plasmid DNA (pDNA) for transcript replacement and vaccination therapy.

Youn H, Chung JK - Expert Opin Biol Ther (2015)

Bottom Line: Conversely, gene delivery using plasmid DNA (pDNA) is considered safer, but its transfection efficiency is much lower than virus-mediated gene transfer.Notable advantages include no risk of integration into the genomic DNA, adjustable gene expression and easier modulation of the immune system.By reducing or utilizing the immunogenic properties, mRNA offers a promising tool for gene/or transcript replacement.

View Article: PubMed Central - PubMed

Affiliation: Seoul National University, College of Medicine, Department of Nuclear Medicine , 103 Daehak-ro, Jongno-gu, Seoul 110-799 , Korea +82 2 2072 3341 ; +82 2 745 7690 ; jkchung@snu.ac.kr.

ABSTRACT

Introduction: Current gene therapy involves replacement of defective gene by delivery of healthy genetic material to precede normal function. Virus-mediated gene delivery is the most successful and efficient method for gene therapy, but it has been challenged due to serious safety concerns. Conversely, gene delivery using plasmid DNA (pDNA) is considered safer, but its transfection efficiency is much lower than virus-mediated gene transfer. Recently, mRNA has been suggested as an alternative option to avoid undesired insertion of delivered DNA sequences with higher transfection efficiency and stability.

Area covered: In this review, we summarize the currently available strategies of mRNA modification to increase the therapeutic efficacy; we also highlight the recent improvements of mRNA delivery for in vivo applications of gene therapy.

Expert opinion: The use of mRNA-based gene transfer could indeed be a promising new strategy for gene therapy. Notable advantages include no risk of integration into the genomic DNA, adjustable gene expression and easier modulation of the immune system. By reducing or utilizing the immunogenic properties, mRNA offers a promising tool for gene/or transcript replacement.

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Nucleoside modification of mRNA for immune escape.
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Figure 0002: Nucleoside modification of mRNA for immune escape.

Mentions: The use of modified nucleosides (Figure 2), such as 2’-O methyl nucleoside for in vitro transcription, shows dramatic suppression of TLR-mediated DC activation [38], but the effects of modified nucleosides on the TLR-independent immune response are still unknown. As many modified nucleosides are present in mammalian RNAs, such as pseudouridine, 2-thiouridine, 5-methylcytidine, 6-methyladenosine, inosine and many 2’-O-methylated nucleosides at the 5’-terminal cap, these nucleosides can be used for modified mRNA to reduce the immune reaction [3].


Modified mRNA as an alternative to plasmid DNA (pDNA) for transcript replacement and vaccination therapy.

Youn H, Chung JK - Expert Opin Biol Ther (2015)

Nucleoside modification of mRNA for immune escape.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4696419&req=5

Figure 0002: Nucleoside modification of mRNA for immune escape.
Mentions: The use of modified nucleosides (Figure 2), such as 2’-O methyl nucleoside for in vitro transcription, shows dramatic suppression of TLR-mediated DC activation [38], but the effects of modified nucleosides on the TLR-independent immune response are still unknown. As many modified nucleosides are present in mammalian RNAs, such as pseudouridine, 2-thiouridine, 5-methylcytidine, 6-methyladenosine, inosine and many 2’-O-methylated nucleosides at the 5’-terminal cap, these nucleosides can be used for modified mRNA to reduce the immune reaction [3].

Bottom Line: Conversely, gene delivery using plasmid DNA (pDNA) is considered safer, but its transfection efficiency is much lower than virus-mediated gene transfer.Notable advantages include no risk of integration into the genomic DNA, adjustable gene expression and easier modulation of the immune system.By reducing or utilizing the immunogenic properties, mRNA offers a promising tool for gene/or transcript replacement.

View Article: PubMed Central - PubMed

Affiliation: Seoul National University, College of Medicine, Department of Nuclear Medicine , 103 Daehak-ro, Jongno-gu, Seoul 110-799 , Korea +82 2 2072 3341 ; +82 2 745 7690 ; jkchung@snu.ac.kr.

ABSTRACT

Introduction: Current gene therapy involves replacement of defective gene by delivery of healthy genetic material to precede normal function. Virus-mediated gene delivery is the most successful and efficient method for gene therapy, but it has been challenged due to serious safety concerns. Conversely, gene delivery using plasmid DNA (pDNA) is considered safer, but its transfection efficiency is much lower than virus-mediated gene transfer. Recently, mRNA has been suggested as an alternative option to avoid undesired insertion of delivered DNA sequences with higher transfection efficiency and stability.

Area covered: In this review, we summarize the currently available strategies of mRNA modification to increase the therapeutic efficacy; we also highlight the recent improvements of mRNA delivery for in vivo applications of gene therapy.

Expert opinion: The use of mRNA-based gene transfer could indeed be a promising new strategy for gene therapy. Notable advantages include no risk of integration into the genomic DNA, adjustable gene expression and easier modulation of the immune system. By reducing or utilizing the immunogenic properties, mRNA offers a promising tool for gene/or transcript replacement.

Show MeSH