mRNA trans-splicing in gene therapy for genetic diseases.

Details

Serval ID
serval:BIB_9DC51B8ACB28
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Title
mRNA trans-splicing in gene therapy for genetic diseases.
Journal
Wiley interdisciplinary reviews. RNA
Author(s)
Berger A., Maire S., Gaillard M.C., Sahel J.A., Hantraye P., Bemelmans A.P.
ISSN
1757-7012 (Electronic)
ISSN-L
1757-7004
Publication state
Published
Issued date
07/2016
Peer-reviewed
Oui
Volume
7
Number
4
Pages
487-498
Language
english
Notes
Publication types: Journal Article ; Review ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Spliceosome-mediated RNA trans-splicing, or SMaRT, is a promising strategy to design innovative gene therapy solutions for currently intractable genetic diseases. SMaRT relies on the correction of mutations at the post-transcriptional level by modifying the mRNA sequence. To achieve this, an exogenous RNA is introduced into the target cell, usually by means of gene transfer, to induce a splice event in trans between the exogenous RNA and the target endogenous pre-mRNA. This produces a chimeric mRNA composed partly of exons of the latter, and partly of exons of the former, encoding a sequence free of mutations. The principal challenge of SMaRT technology is to achieve a reaction as complete as possible, i.e., resulting in 100% repairing of the endogenous mRNA target. The proof of concept of SMaRT feasibility has already been established in several models of genetic diseases caused by recessive mutations. In such cases, in fact, the repair of only a portion of the mutant mRNA pool may be sufficient to obtain a significant therapeutic effect. However in the case of dominant mutations, the target cell must be freed from the majority of mutant mRNA copies, requiring a highly efficient trans-splicing reaction. This likely explains why only a few examples of SMaRT approaches targeting dominant mutations are reported in the literature. In this review, we explain in details the mechanism of trans-splicing, review the different strategies that are under evaluation to lead to efficient trans-splicing, and discuss the advantages and limitations of SMaRT. WIREs RNA 2016, 7:487-498. doi: 10.1002/wrna.1347 For further resources related to this article, please visit the WIREs website.
Keywords
Animals, Genetic Diseases, Inborn/therapy, Genetic Therapy/methods, Humans, RNA, Messenger/metabolism, Trans-Splicing
Pubmed
Web of science
Open Access
Yes
Create date
08/07/2020 11:26
Last modification date
16/07/2020 8:43
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