ArticleNature biotechnology2015
Massively parallel high-order combinatorial genetics in human cells.
Article in Nature biotechnology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 65 citations in OpenAlex.
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- A unified genetic perturbation language for human cellular programming.bioRxiv : the preprint server for biology · 2025Article
- Combinatorial protein engineering identifies potent CRISPR activators with reduced toxicity.Nature communications · 2025Article
- Mitigation of Doxorubicin Cardiotoxicity With Synergistic miRNA Combinations Identified Using Combinatorial Genetics en masse (CombiGEM).JACC. CardioOncology · 2025Article
- Combinatorial CRISPR screen revealseLife · 2025Article
- Engineered CRISPR-Cas12a for higher-order combinatorial chromatin perturbations.Nature biotechnology · 2025Article
- Automated Design of Oligopools and Rapid Analysis of Massively Parallel Barcoded Measurements.ACS synthetic biology · 2024Article
- Review
- Encoding Genetic Circuits with DNA Barcodes Paves the Way for High-Throughput Profiling of Dose-Response Curves of Metabolite Biosensors.Methods in molecular biology (Clifton, N.J.) · 2024Article
- CRISPR screening in hematology research: from bulk to single-cell level.Journal of hematology & oncology · 2023Review
- Improved Combinatorial Assembly and Barcode Sequencing for Gene-Sized DNA Constructs.ACS synthetic biology · 2023Article
- Ancestral library identifies conserved reprogrammable liver motif on AAV capsid.Cell reports. Medicine · 2022Article
- Combinatorial genetics methods for discovering high-order regulatory combinations and engineering genetic drivers for neural differentiation.Neural regeneration research · 2021Review
- High-throughput 5' UTR engineering for enhanced protein production in non-viral gene therapies.Nature communications · 2021Article
- Extensible combinatorial CRISPR screening in mammalian cells.STAR protocols · 2021Article
- Strategies for simultaneous and successive delivery of RNA.Journal of molecular medicine (Berlin, Germany) · 2020Article
- A High-Content Screen Identifies MicroRNAs That Regulate Liver Repopulation After Injury in Mice.Gastroenterology · 2020Article
- An improved platform for functional assessment of large protein libraries in mammalian cells.Nucleic acids research · 2020Article
- A 'poly-transfection' method for rapid, one-pot characterization and optimization of genetic systems.Nucleic acids research · 2019Article
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5 authors at 2 institutions in 1 country.
Funding
Abstract
The systematic functional analysis of combinatorial genetics has been limited by the throughput that can be achieved and the order of complexity that can be studied. To enable massively parallel characterization of genetic combinations in human cells, we developed a technology for rapid, scalable assembly of high-order barcoded combinatorial genetic libraries that can be quantified with high-throughput sequencing. We applied this technology, combinatorial genetics en masse (CombiGEM), to create high-coverage libraries of 1,521 two-wise and 51,770 three-wise barcoded combinations of 39 human microRNA (miRNA) precursors. We identified miRNA combinations that synergistically sensitize drug-resistant cancer cells to chemotherapy and/or inhibit cancer cell proliferation, providing insights into complex miRNA networks. More broadly, our method will enable high-throughput profiling of multifactorial genetic combinations that regulate phenotypes of relevance to biomedicine, biotechnology and basic science.
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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.