The use of antisense molecules for splicing modulation as a treatment for genetic disorders
https://doi.org/10.25557/2073-7998.2023.02.3-17
Abstract
Splicing is a complex stage of gene expression regulated by many cis-elements represented by the specific pre-mRNA sequence motifs and trans-elements that are proteins and ribonucleoprotein complexes. Splicing disruption often leads to genetic disorders. A lot of pathogenic variants causing aberrant splicing are described in databases for human mutations, demonstrating a need for the development of the effective and safe splicing modulation tools and its application. Recent studies of the fundamental splicing regulation processes allow researchers to develop few tools for splicing modulation in order to be used as a therapeutic. In this review we describe the experience in antisense molecules application in vitro and in vivo according to the pathogenesis of the splicing disruption and affected components of its regulation; advantages and disadvantages of antisense oligonucleotides, modified small nuclear RNAs, spliceosome-mediated mRNA trans-splicing technology as a tools of therapy and tools for its delivery to the cells are also discussed.
Supporting agencies: The study was supported by the state task of the Ministry of Science and Higher Education of the Russian Federation
About the Authors
A. S. Galushkin
Research Centre for Medical Genetics
Russian Federation
Russian Federation
Artur S. Galushkin
115522
1, Moskvorechye str.
Moscow
A. Yu. Nekrasov
Research Centre for Medical Genetics
Russian Federation
Russian Federation
115522
1, Moskvorechye str.
Moscow
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Review
For citations:
Galushkin A.S., Nekrasov A.Yu. The use of antisense molecules for splicing modulation as a treatment for genetic disorders. Medical Genetics. 2023;22(2):3-17. (In Russ.) https://doi.org/10.25557/2073-7998.2023.02.3-17
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