Trans-acting aptazyme for conditional gene knockdown in eukaryotic cells
Trans-acting hammerhead ribozyme inherits the advantages of being the smallest and best-characterized RNA-cleaving ribozyme, offering high modularity and the ability to cleave any desired sequence without the aid of any protein, as long as the target sequence contains a cleavage site. However, achie...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-09-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253123001877 |
| _version_ | 1797769770584506368 |
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| author | Shan Zhou Meiyi Chen Yi Yuan Yan Xu Qinlin Pu Xilei Ai Shuai Liu Feng Du Xin Huang Juan Dong Xin Cui Zhuo Tang |
| author_facet | Shan Zhou Meiyi Chen Yi Yuan Yan Xu Qinlin Pu Xilei Ai Shuai Liu Feng Du Xin Huang Juan Dong Xin Cui Zhuo Tang |
| author_sort | Shan Zhou |
| collection | DOAJ |
| description | Trans-acting hammerhead ribozyme inherits the advantages of being the smallest and best-characterized RNA-cleaving ribozyme, offering high modularity and the ability to cleave any desired sequence without the aid of any protein, as long as the target sequence contains a cleavage site. However, achieving precise control over the trans-acting hammerhead ribozyme would enable safer and more accurate regulation of gene expression. Herein, we described an intracellular selection of hammerhead aptazyme that contains a theophylline aptamer on stem II based on toxin protein IbsC. Based on the intracellular selection, we obtained three new cis-acting hammerhead aptazymes. Moreover, the corresponding trans-acting aptazymes could be efficiently induced by theophylline to knock down different targeted genes in eukaryotic cells. Notably, the best one, T195, exhibited a ligand-dependent and dose-dependent response to theophylline, and the cleavage efficiency could be enhanced by incorporating multiplex aptazymes. |
| first_indexed | 2024-03-12T21:13:48Z |
| format | Article |
| id | doaj.art-49fd6d324f714b53a66d4ff6e1fef7a9 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-03-12T21:13:48Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-49fd6d324f714b53a66d4ff6e1fef7a92023-07-30T04:22:20ZengElsevierMolecular Therapy: Nucleic Acids2162-25312023-09-0133367375Trans-acting aptazyme for conditional gene knockdown in eukaryotic cellsShan Zhou0Meiyi Chen1Yi Yuan2Yan Xu3Qinlin Pu4Xilei Ai5Shuai Liu6Feng Du7Xin Huang8Juan Dong9Xin Cui10Zhuo Tang11Natural Products Research Center, Chengdu Institution of Biology, Chinese Academy of Sciences, Chengdu 610041, P.R. China; University of Chinese Academy of Sciences, Beijing 100049, P.R. ChinaNatural Products Research Center, Chengdu Institution of Biology, Chinese Academy of Sciences, Chengdu 610041, P.R. ChinaNatural Products Research Center, Chengdu Institution of Biology, Chinese Academy of Sciences, Chengdu 610041, P.R. ChinaNatural Products Research Center, Chengdu Institution of Biology, Chinese Academy of Sciences, Chengdu 610041, P.R. ChinaNatural Products Research Center, Chengdu Institution of Biology, Chinese Academy of Sciences, Chengdu 610041, P.R. ChinaNatural Products Research Center, Chengdu Institution of Biology, Chinese Academy of Sciences, Chengdu 610041, P.R. ChinaNatural Products Research Center, Chengdu Institution of Biology, Chinese Academy of Sciences, Chengdu 610041, P.R. ChinaNatural Products Research Center, Chengdu Institution of Biology, Chinese Academy of Sciences, Chengdu 610041, P.R. ChinaNatural Products Research Center, Chengdu Institution of Biology, Chinese Academy of Sciences, Chengdu 610041, P.R. ChinaNatural Products Research Center, Chengdu Institution of Biology, Chinese Academy of Sciences, Chengdu 610041, P.R. ChinaNatural Products Research Center, Chengdu Institution of Biology, Chinese Academy of Sciences, Chengdu 610041, P.R. ChinaNatural Products Research Center, Chengdu Institution of Biology, Chinese Academy of Sciences, Chengdu 610041, P.R. China; Corresponding author. Zhuo Tang, Natural Products Research Center, Chengdu Institution of Biology, Chinese Academy of Sciences, Chengdu 610041, P.R. China.Trans-acting hammerhead ribozyme inherits the advantages of being the smallest and best-characterized RNA-cleaving ribozyme, offering high modularity and the ability to cleave any desired sequence without the aid of any protein, as long as the target sequence contains a cleavage site. However, achieving precise control over the trans-acting hammerhead ribozyme would enable safer and more accurate regulation of gene expression. Herein, we described an intracellular selection of hammerhead aptazyme that contains a theophylline aptamer on stem II based on toxin protein IbsC. Based on the intracellular selection, we obtained three new cis-acting hammerhead aptazymes. Moreover, the corresponding trans-acting aptazymes could be efficiently induced by theophylline to knock down different targeted genes in eukaryotic cells. Notably, the best one, T195, exhibited a ligand-dependent and dose-dependent response to theophylline, and the cleavage efficiency could be enhanced by incorporating multiplex aptazymes.http://www.sciencedirect.com/science/article/pii/S2162253123001877MT: Oligonucleotides: Therapies and Applicationshammerhead ribozymetrans-actingaptazymetheophyllinegene knockdown |
| spellingShingle | Shan Zhou Meiyi Chen Yi Yuan Yan Xu Qinlin Pu Xilei Ai Shuai Liu Feng Du Xin Huang Juan Dong Xin Cui Zhuo Tang Trans-acting aptazyme for conditional gene knockdown in eukaryotic cells Molecular Therapy: Nucleic Acids MT: Oligonucleotides: Therapies and Applications hammerhead ribozyme trans-acting aptazyme theophylline gene knockdown |
| title | Trans-acting aptazyme for conditional gene knockdown in eukaryotic cells |
| title_full | Trans-acting aptazyme for conditional gene knockdown in eukaryotic cells |
| title_fullStr | Trans-acting aptazyme for conditional gene knockdown in eukaryotic cells |
| title_full_unstemmed | Trans-acting aptazyme for conditional gene knockdown in eukaryotic cells |
| title_short | Trans-acting aptazyme for conditional gene knockdown in eukaryotic cells |
| title_sort | trans acting aptazyme for conditional gene knockdown in eukaryotic cells |
| topic | MT: Oligonucleotides: Therapies and Applications hammerhead ribozyme trans-acting aptazyme theophylline gene knockdown |
| url | http://www.sciencedirect.com/science/article/pii/S2162253123001877 |
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