ArticleNucleic acids research2020
A single amino acid switch converts the Sleeping Beauty transposase into an efficient unidirectional excisionase with utility in stem cell reprogramming.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 16 citations in OpenAlex.
- Structure-based recasting of a mammalian DNA transpososome as an obligate heterodimer.bioRxiv : the preprint server for biology · 2026Article
- The relationship between DNA damage and repair and the occurrence and development of disease.Frontiers in genetics · 2026Review
- XPRESSO: Rapid genetic engineering of human pluripotent stem cells for durable overexpression using a modular anti-silencing vector.Stem cell reports · 2025Article
- Engineering of BZ transposase and transposon donor vector for enhanced efficiency and safety in gene delivery applications.Nucleic acids research · 2025Article
- Unveiling the mysteries of extrachromosomal circular DNA: from generation to clinical relevance in human cancers and health.Molecular cancer · 2024Review
- A novel hyperactive variant of theMolecular therapy. Nucleic acids · 2024Article
- Reprogramming stem cells in regenerative medicine.Smart medicine · 2022Review
- Structural insights into the evolution of the RAG recombinase.Nature reviews. Immunology · 2022Review
- Engineered Sleeping Beauty transposase redirects transposon integration away from genes.Nucleic acids research · 2022Article
- Review
- Contemporary Transposon Tools: A Review and Guide through Mechanisms and Applications ofInternational journal of molecular sciences · 2021Review
- Jumping Ahead withViruses · 2021Review
- Engineering cell fate: Applying synthetic biology to cellular reprogramming.Current opinion in systems biology · 2020Article
- Potential of transposon-mediated cellular reprogramming towards cell-based therapies.World journal of stem cells · 2020Review
- Review
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Sleeping Beauty (SB) transposon is an advanced tool for genetic engineering and a useful model to investigate cut-and-paste DNA transposition in vertebrate cells. Here, we identify novel SB transposase mutants that display efficient and canonical excision but practically unmeasurable genomic re-integration. Based on phylogenetic analyses, we establish compensating amino acid replacements that fully rescue the integration defect of these mutants, suggesting epistasis between these amino acid residues. We further show that the transposons excised by the exc+/int- transposase mutants form extrachromosomal circles that cannot undergo a further round of transposition, thereby representing dead-end products of the excision reaction. Finally, we demonstrate the utility of the exc+/int- transposase in cassette removal for the generation of reprogramming factor-free induced pluripotent stem cells. Lack of genomic integration and formation of transposon circles following excision is reminiscent of signal sequence removal during V(D)J recombination, and implies that cut-and-paste DNA transposition can be converted to a unidirectional process by a single amino acid change.
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