ArticleRNA (New York, N.Y.)2012
An in vivo selection method to optimize trans-splicing ribozymes.
Article in RNA (New York, N.Y.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Repair of MutatedCancers · 2025Article
- Efficient circular RNA synthesis for potent rolling circle translation.Nature biomedical engineering · 2025Article
- Programmable trans-splicing riboregulators for complex cellular logic computation.Nature chemical biology · 2025Article
- Importance of pre-mRNA splicing and its study tools in plants.Advanced biotechnology · 2024Review
- Group I Intron as a Potential Target for Antifungal Compounds: Development of aMolecules (Basel, Switzerland) · 2023Article
- Therapeutic applications of trans-splicing.British medical bulletin · 2020Article
- Intracellular selection of trans-cleaving hammerhead ribozymes.Nucleic acids research · 2019Article
- RNA Trans-Splicing Modulation via Antisense Molecule Interference.International journal of molecular sciences · 2018Article
- Site-Selective RNA Splicing Nanozyme: DNAzyme and RtcB Conjugates on a Gold Nanoparticle.ACS chemical biology · 2018Article
- Design and Experimental Evolution of trans-Splicing Group I Intron Ribozymes.Molecules (Basel, Switzerland) · 2017Review
- Article
- Increased efficiency of evolved group I intron spliceozymes by decreased side product formation.RNA (New York, N.Y.) · 2015Article
- Trans-splicing with the group I intron ribozyme from Azoarcus.RNA (New York, N.Y.) · 2014Article
- Article
- Article
- Low selection pressure aids the evolution of cooperative ribozyme mutations in cells.The Journal of biological chemistry · 2013Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Group I intron ribozymes can repair mutated mRNAs by replacing the 3'-terminal portion of the mRNA with their own 3'-exon. This trans-splicing reaction has the potential to treat genetic disorders and to selectively kill cancer cells or virus-infected cells. However, these ribozymes have not yet been used in therapy, partially due to a low in vivo trans-splicing efficiency. Previous strategies to improve the trans-splicing efficiencies focused on designing and testing individual ribozyme constructs. Here we describe a method that selects the most efficient ribozymes from millions of ribozyme variants. This method uses an in vivo rescue assay where the mRNA of an inactivated antibiotic resistance gene is repaired by trans-splicing group I intron ribozymes. Bacterial cells that express efficient trans-splicing ribozymes are able to grow on medium containing the antibiotic chloramphenicol. We randomized a 5'-terminal sequence of the Tetrahymena thermophila group I intron and screened a library with 9 × 10⁶ ribozyme variants for the best trans-splicing activity. The resulting ribozymes showed increased trans-splicing efficiency and help the design of efficient trans-splicing ribozymes for different sequence contexts. This in vivo selection method can now be used to optimize any sequence in trans-splicing ribozymes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.