ArticleCell systems2025
Model-guided design of microRNA-based gene circuits supports precise dosage of transgenic cargoes into diverse primary cells.
Article in Cell systems, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Fluorescent protein ticker tape (FPTT): Multiplexed recording of transcriptional dynamics in living cells and in vivo.Science advances · 2026Article
- Programmable promoter editing for precise control of transgene expression.Nature biotechnology · 2026Article
- Promoter editing generates stable setpoints of gene expression.Nature biotechnology · 2026Article
- Temporal control of midline crossing via incoherent feedforward and feedback loops regulating Robo3.iScience · 2026Article
- Current Progress and Future Outlook for Synthetic Gene Circuits in Cardiovascular Therapy.Biomolecules · 2026Review
- Engineering high-titer lentiviral vectors for robust expression of RNA-based gene circuits.bioRxiv : the preprint server for biology · 2026Article
- 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
- GCAD: A Computational Framework for Mammalian Genetic Program Computer-Aided Design.ACS synthetic biology · 2026Article
- Programmable nanobody circuits for cell selection.bioRxiv : the preprint server for biology · 2026Article
- Integrating synthetic biology to understand and engineer the heart, lung, blood, and sleep systems.Cell systems · 2025Review
- miRNA modules for precise, tunable control of gene expression.bioRxiv : the preprint server for biology · 2025Article
- Article
- Tunable, proteolytic dosage control of CRISPR-Cas systems enables precise gene therapy for dosage sensitive disorders.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
- Human Synthetic Biology and Programmable Gene Regulation Control.Annual review of genomics and human genetics · 2025Review
- High-resolution profiling reveals coupled transcriptional and translational regulation of transgenes.Nucleic acids research · 2025Article
- Compact transcription factor cassettes generate functional, engraftable motor neurons by direct conversion.Cell systems · 2025Article
- High-resolution profiling reveals coupled transcriptional and translational regulation of transgenes.bioRxiv : the preprint server for biology · 2024Article
- Programmable promoter editing for precise control of transgene expression.bioRxiv : the preprint server for biology · 2024Article
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6 authors.
Funding
Abstract
In a therapeutic context, supraphysiological expression of transgenes can compromise engineered phenotypes and lead to toxicity. To ensure a narrow range of transgene expression, we developed a single-transcript, microRNA-based incoherent feedforward loop called compact microRNA-mediated attenuator of noise and dosage (ComMAND). We experimentally tuned the ComMAND output profile, and we modeled the system to explore additional tuning strategies. By comparing ComMAND to two-gene implementations, we demonstrate the precise control afforded by the single-transcript architecture, particularly at low copy numbers. We show that ComMAND tightly regulates transgene expression from lentiviruses and precisely controls expression in primary human T cells, primary rat neurons, primary mouse embryonic fibroblasts, and human induced pluripotent stem cells. Finally, ComMAND effectively sets levels of the clinically relevant transgenes frataxin (FXN) and fragile X messenger ribonucleoprotein 1 (Fmr1) within a narrow window. Overall, ComMAND is a compact tool well suited to precisely specify the expression of therapeutic cargoes. A record of this paper's transparent peer review process is included in the supplemental information.
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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.