ArticleNature biotechnology2026
Evolution-guided protein design of IscB for persistent epigenome editing in vivo.
Article in Nature biotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Structure-guided discovery and engineering of miniature CRISPR-Cas12m for epigenome editing.Nature structural & molecular biology · 2026Article
- Compact 9dBEs Enable Efficient and Precise Genome Editing in Mammalian Cells and In Vivo.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- MYB transcription factors in plant cold stress adaptation: integrating phylogeny, signaling networks, and metabolic regulation.Physiology and molecular biology of plants : an international journal of functional plant biology · 2026Review
- Epigenetic editing approaches maturity: AI-driven precision design, delivery innovation, and the road to clinical translation.Clinical epigenetics · 2026Review
- Structure basis for single-strand nucleic acid targeting by IscB and variants.Nucleic acids research · 2026Article
- Clinical translation of epigenome editing technologies.Current opinion in biomedical engineering · 2026Article
- Rewriting the epigenome: CRISPR tools for biological discovery and therapeutics.Current opinion in biomedical engineering · 2026Article
- Resurrecting a miniature Cas9 ancestor for genome and epigenome editing.Nature biotechnology · 2026Article
- Evolution-guided protein design of IscB for persistent epigenome editing in vivo.Nature biotechnology · 2026Article
- Structural insight into IscB's RNA-lid-based inactivation mechanism.Nature structural & molecular biology · 2026Article
- Engineered TnpB genome editors for plants and human cells identified by ribonucleoprotein mutational scanning.Nature biotechnology · 2026Article
- Structure basis for single-strand nucleic acid targeting by IscB and variants.bioRxiv : the preprint server for biology · 2026Article
- mRNA-engineered CRISPR-Cas epigenetic editors enable durable and efficient gene silencingInnovation (Cambridge (Mass.)) · 2026Article
- Epigenetic editing: from concept to clinic.Nature reviews. Drug discovery · 2026Review
- Harnessing artificial intelligence to advance CRISPR-based genome editing technologies.Nature reviews. Genetics · 2026Review
- Engineering hypercompact IscB nucleases for efficient and versatile genome editing in rice.Genome biology · 2026Article
- Epigenome editing based treatment: Progresses and challenges.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- Transposon-derived genome editors in plants: from compact nucleases to large-fragment integration and regeneration strategies.Engineering in life sciences · 2026Review
- Loop engineering of AtCas9 for effective and broad genome editing.Cell insight · 2025Article
- Engineering a CRISPR-associated IscB system for developing miniature genome-editing tools in human cells and mouse embryos.Nature communications · 2025Article
Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Naturally existing enzymes have been adapted for a variety of molecular technologies, with enhancements or modifications to the enzymes introduced to improve the desired function; however, it is difficult to engineer variants with enhanced activity while maintaining specificity. Here we engineer the compact Obligate Mobile Element Guided Activity (OMEGA) RNA-guided endonuclease IscB and its guiding RNA (ωRNA) by combining ortholog screening, structure-guided protein domain design and RNA engineering, and deep learning-based structure prediction to generate an improved variant, NovaIscB. We show that the compact NovaIscB achieves up to 40% indel activity (~100-fold improvement over wild-type OgeuIscB) on the human genome with improved specificity relative to existing IscBs. We further show that NovaIscB can be fused with a methyltransferase to create a programmable transcriptional repressor, OMEGAoff, that is compact enough to be packaged in a single adeno-associated virus vector for persistent in vivo gene repression. This study highlights the power of combining natural diversity with protein engineering to design enhanced enzymes for molecular biology applications.
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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.