Development of Engineered-U1 snRNA Therapies: Current Status
Splicing of pre-mRNA is a crucial regulatory stage in the pathway of gene expression. The majority of human genes that encode proteins undergo alternative pre-mRNA splicing and mutations that affect splicing are more prevalent than previously thought. Targeting aberrant RNA(s) may thus provide an op...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/19/14617 |
| _version_ | 1797575777635532800 |
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| author | Mariana Gonçalves Juliana Inês Santos Maria Francisca Coutinho Liliana Matos Sandra Alves |
| author_facet | Mariana Gonçalves Juliana Inês Santos Maria Francisca Coutinho Liliana Matos Sandra Alves |
| author_sort | Mariana Gonçalves |
| collection | DOAJ |
| description | Splicing of pre-mRNA is a crucial regulatory stage in the pathway of gene expression. The majority of human genes that encode proteins undergo alternative pre-mRNA splicing and mutations that affect splicing are more prevalent than previously thought. Targeting aberrant RNA(s) may thus provide an opportunity to correct faulty splicing and potentially treat numerous genetic disorders. To that purpose, the use of engineered U1 snRNA (either modified U1 snRNAs or exon-specific U1s—ExSpeU1s) has been applied as a potentially therapeutic strategy to correct splicing mutations, particularly those affecting the 5′ splice-site (5′ss). Here we review and summarize a vast panoply of studies that used either modified U1 snRNAs or ExSpeU1s to mediate gene therapeutic correction of splicing defects underlying a considerable number of genetic diseases. We also focus on the pre-clinical validation of these therapeutic approaches both in vitro and in vivo, and summarize the main obstacles that need to be overcome to allow for their successful translation to clinic practice in the future. |
| first_indexed | 2024-03-10T21:44:05Z |
| format | Article |
| id | doaj.art-d26cea51014f44468692230e8d671cbc |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T21:44:05Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d26cea51014f44468692230e8d671cbc2023-11-19T14:29:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124191461710.3390/ijms241914617Development of Engineered-U1 snRNA Therapies: Current StatusMariana Gonçalves0Juliana Inês Santos1Maria Francisca Coutinho2Liliana Matos3Sandra Alves4Research and Development Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, INSA I.P., Rua Alexandre Herculano, 321, 4000-055 Porto, PortugalResearch and Development Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, INSA I.P., Rua Alexandre Herculano, 321, 4000-055 Porto, PortugalResearch and Development Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, INSA I.P., Rua Alexandre Herculano, 321, 4000-055 Porto, PortugalResearch and Development Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, INSA I.P., Rua Alexandre Herculano, 321, 4000-055 Porto, PortugalResearch and Development Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, INSA I.P., Rua Alexandre Herculano, 321, 4000-055 Porto, PortugalSplicing of pre-mRNA is a crucial regulatory stage in the pathway of gene expression. The majority of human genes that encode proteins undergo alternative pre-mRNA splicing and mutations that affect splicing are more prevalent than previously thought. Targeting aberrant RNA(s) may thus provide an opportunity to correct faulty splicing and potentially treat numerous genetic disorders. To that purpose, the use of engineered U1 snRNA (either modified U1 snRNAs or exon-specific U1s—ExSpeU1s) has been applied as a potentially therapeutic strategy to correct splicing mutations, particularly those affecting the 5′ splice-site (5′ss). Here we review and summarize a vast panoply of studies that used either modified U1 snRNAs or ExSpeU1s to mediate gene therapeutic correction of splicing defects underlying a considerable number of genetic diseases. We also focus on the pre-clinical validation of these therapeutic approaches both in vitro and in vivo, and summarize the main obstacles that need to be overcome to allow for their successful translation to clinic practice in the future.https://www.mdpi.com/1422-0067/24/19/14617U1 snRNA (small nuclear RNA)-based therapiesmodified U1 snRNAsexon-specific U1 snRNAs (ExSpeU1s)5′ splice-site (5′ss)splicing mutationssplicing correction |
| spellingShingle | Mariana Gonçalves Juliana Inês Santos Maria Francisca Coutinho Liliana Matos Sandra Alves Development of Engineered-U1 snRNA Therapies: Current Status International Journal of Molecular Sciences U1 snRNA (small nuclear RNA)-based therapies modified U1 snRNAs exon-specific U1 snRNAs (ExSpeU1s) 5′ splice-site (5′ss) splicing mutations splicing correction |
| title | Development of Engineered-U1 snRNA Therapies: Current Status |
| title_full | Development of Engineered-U1 snRNA Therapies: Current Status |
| title_fullStr | Development of Engineered-U1 snRNA Therapies: Current Status |
| title_full_unstemmed | Development of Engineered-U1 snRNA Therapies: Current Status |
| title_short | Development of Engineered-U1 snRNA Therapies: Current Status |
| title_sort | development of engineered u1 snrna therapies current status |
| topic | U1 snRNA (small nuclear RNA)-based therapies modified U1 snRNAs exon-specific U1 snRNAs (ExSpeU1s) 5′ splice-site (5′ss) splicing mutations splicing correction |
| url | https://www.mdpi.com/1422-0067/24/19/14617 |
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