ArticleProceedings of the National Academy of Sciences of the United States of America2021
A versatile platform for locus-scale genome rewriting and verification.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 70 citations in OpenAlex.
- Robust regulatory interplay of enhancers, facilitators, and promoters in a native chromatin context.Cell · 2026Article
- Synthetic Regulatory Genomics.Annual review of genomics and human genetics · 2026Review
- STRAIGHT-IN Dual: a platform for dual single-copy integrations of DNA payloads and gene circuits into human induced pluripotent stem cells.Nature biomedical engineering · 2026Article
- Facilitators may represent a new class of regulatory elements.Current opinion in genetics & development · 2026Review
- Improved vector toolkit for genome writing in mammalian cells.bioRxiv : the preprint server for biology · 2026Article
- Programmable nanobody circuits for cell selection.bioRxiv : the preprint server for biology · 2026Article
- Review
- Synthetic rewriting technologies in mammalian cells.Nature communications · 2026Review
- Genome writing and Targeted Delivery of thebioRxiv : the preprint server for biology · 2026Article
- Integrating synthetic biology to understand and engineer the heart, lung, blood, and sleep systems.Cell systems · 2025Review
- Editing stem cell genomes at scale to measure variant effects in diverse cell and genetic contexts.medRxiv : the preprint server for health sciences · 2025Article
- Iterative improvement of deep learning models using synthetic regulatory genomics.Genome research · 2025Article
- Genome writing to dissect consequences of SVA retrotransposon disease X-Linked Dystonia Parkinsonism.bioRxiv : the preprint server for biology · 2025Article
- Human Genome REWRITE for Off-the-Shelf Stem Cells Reveals an "Epigenetic Ghost".bioRxiv : the preprint server for biology · 2025Article
- STRAIGHT-IN Dual: a platform for dual, single-copy integrations of DNA payloads and gene circuits into human induced pluripotent stem cell.bioRxiv : the preprint server for biology · 2025Article
- De novo assembly and delivery of synthetic megabase-scale human DNA into mouse early embryos.Nature methods · 2025Article
- The design and engineering of synthetic genomes.Nature reviews. Genetics · 2025Review
- Article
- Termination sequence between an inducible promoter and ubiquitous chromatin opening element (UCOE) reduces gene expression leakage and silencing.Journal of biological engineering · 2025Article
- CutIn: a ready-to-use construct for rapid generation of urgently needed transgenic cell lines in emerging infection research.Functional & integrative genomics · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Routine rewriting of loci associated with human traits and diseases would facilitate their functional analysis. However, existing DNA integration approaches are limited in terms of scalability and portability across genomic loci and cellular contexts. We describe Big-IN, a versatile platform for targeted integration of large DNAs into mammalian cells. CRISPR/Cas9-mediated targeting of a landing pad enables subsequent recombinase-mediated delivery of variant payloads and efficient positive/negative selection for correct clones in mammalian stem cells. We demonstrate integration of constructs up to 143 kb, and an approach for one-step scarless delivery. We developed a staged pipeline combining PCR genotyping and targeted capture sequencing for economical and comprehensive verification of engineered stem cells. Our approach should enable combinatorial interrogation of genomic functional elements and systematic locus-scale analysis of genome function.
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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 Socratic graph.