Use of modified U1 snRNA for rescue from exon skipping caused by 5' splice site mutation of human CTSA gene
| Project/Area Number |
16K08235
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | The University of Tokushima |
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Principal Investigator |
YAMAZAKI Naoshi 徳島大学, 大学院医歯薬学研究部(薬学域), 准教授 (20271083)
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| Co-Investigator(Kenkyū-buntansha) |
南川 典昭 徳島大学, 大学院医歯薬学研究部(薬学域), 教授 (40209820)
伊藤 孝司 徳島大学, 大学院医歯薬学研究部(薬学域), 教授 (00184656)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | スプライス / U1 snRNA / 薬学 / 発現制御 |
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| Outline of Final Research Achievements |
Cathepsin A (CTSA) is a multifunctional lysosomal enzyme, and its hereditary defect causes an autosomal recessive disorder called galactosialidosis. In a certain number of galactosialidosis patients, a base substitution from adenine to guanine is observed at the +3 position of intron 7 (IVS7 +3a>g) of the CTSA gene. With this mutation, a splicing error occurs; and mRNA lacking exon 7 is produced. To produce properly spliced mRNA from the CTSA gene with this mutation, we examined the possible usefulness of modified U1 snRNA that could interact with the mutated 5' splice site. As a result, we succeeded in obtaining improved formation of properly spliced CTSA mRNA from the mutant CTSA gene. Our results suggest the usefulness of modified U1 snRNA for rescue from exon 7 skipping caused by the IVS7 +3a>g mutation of the CTSA gene.
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| Academic Significance and Societal Importance of the Research Achievements |
我々は、ガラクトシアリドーシスの発症原因となるCTSA遺伝子IVS7 +3a>g変異によって起こるRNAスプライス異常を、改変U1 snRNAによって是正できることを培養細胞を用いた実験によって明らかとした．ガラクトシアリドーシスは難病指定されているリソソーム病（ライソゾーム病）の一種であり、現在は対症療法しか存在せず、根本的な治療法は確立されていない．RNAスプライス異常が原因で発症する他の遺伝性疾患においても塩基改変したU1 snRNAを治療に用いる試みが為されている．従って、我々の確立した手法をさらに進展させればガラクトシアリドーシスの有効な治療法開発に繋がることが期待できる．
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Report
(4 results)
Research Products
(14 results)
