mRNA as gene therapeutic: How to control protein expression

For many years, it was generally accepted that mRNA is too unstable to be efficiently used for gene therapy purposes. In the last decade, however, several research groups faced this challenge and not only proved the feasibility of mRNA‐mediated transfection with surprising results regarding transfec...

Full description

Saved in:
Bibliographic Details
Published in:Journal of controlled release 2011-03, Vol.150 (3), p.238-247
Main Authors: Tavernier, Geertrui, Andries, Oliwia, Demeester, Jo, Sanders, Niek N., De Smedt, Stefaan C., Rejman, Joanna
Format: Article
Language:English
Subjects:
Animals
bioactive properties
Biological and medical sciences
Controlled release
CpG islands
Electroporation
Gene therapy
Gene transfer
General pharmacology
genes
half life
Humans
immune response
Immunogenicity
Immunotherapy - methods
Lipoplexes
Medical sciences
messenger RNA
mRNA
mRNA delivery
mRNA vaccines
Neoplasms - therapy
Nuclear barrier
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Poly(A)tail
Polyplexes
protein synthesis
Reviews
RNA, Messenger - genetics
RNA, Messenger - therapeutic use
Transfection
Transfection - methods
Vaccination
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:For many years, it was generally accepted that mRNA is too unstable to be efficiently used for gene therapy purposes. In the last decade, however, several research groups faced this challenge and not only proved the feasibility of mRNA‐mediated transfection with surprising results regarding transfection efficiency and duration of protein expression, but also were able to demonstrate major advantages over the use of pDNA. These advantages will be the first issue discussed in this review, which first of all addresses the notions that mRNA does not need to cross the nuclear barrier to exert its biological activity and in addition lacks CpG motifs, which reduces its immunogenicity. Secondly, it provides insight in the (in)stability of the mRNA molecule, in how mRNA can be modified to increase its half‐life and in the necessities of exogenously produced mRNA to be successfully used in transfection protocols. Furthermore, this review gives an in‐depth overview of the different techniques and vehicles for intracellular mRNA delivery exploited by us and other groups, comprising electroporation, gene gun injection, lipo‐ and polyplexes. Finally, it covers recent literature describing specific applications for mRNA based gene delivery, showing that until now most attention has been paid to vaccination strategies. This review offers a comprehensive overview of current knowledge of the major theoretical as well as practical aspects of mRNA-mediated transfection, showing both its possibilities and its pitfalls and should therefore be useful for a diverse scientific audience. [Display omitted]
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2010.10.020