ArticleNucleic acids research2017
In silico design of context-responsive mammalian promoters with user-defined functionality.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 43 citations in OpenAlex.
- Improving recombinant protein productivity in CHO cells via multi-omics data integration.Bioresources and bioprocessing · 2026Review
- Development and Evaluation of Compact Semi-Synthetic Promoters for Enhanced Antigen Expression in Adenoviral-Vectored Vaccines.Vaccines · 2026Article
- Systematic Evaluation of Vector Sequence Elements in Isogenic CHO Cells for Improved Antibody Production.ACS synthetic biology · 2026Article
- Synthetic promoters developed through a site-specific integration system enhance antibody expression in fed-batch culture.Engineering in life sciences · 2026Article
- Key Challenges and Optimization Practices for Non-clinical Evaluation of AAV based Gene Therapy for Central Nervous System Disease.Pharmaceutical research · 2025Review
- Article
- High-throughput optimization of antibody production in CHO cells by tuning heavy- and light-chain promoter strength.Frontiers in bioengineering and biotechnology · 2025Article
- Targeted UDP-glucose ceramide glucosyltransferase stable overexpression induces a metabolic switch improving cell performance at high cell density.Frontiers in bioengineering and biotechnology · 2025Article
- Cardiocutaneous syndrome is caused by aggregation of iASPP mutants.Cell death discovery · 2024Article
- Article
- Engineered CHO cells as a novel AAV production platform for gene therapy delivery.Scientific reports · 2023Article
- A synthetic transcription platform for programmable gene expression in mammalian cells.Nature communications · 2022Article
- Bioinformatic Design of Dendritic Cell-Specific Synthetic Promoters.ACS synthetic biology · 2022Article
- Control of Multigene Expression Stoichiometry in Mammalian Cells Using Synthetic Promoters.ACS synthetic biology · 2021Article
- A Multifaceted Approach to Optimizing AAV Delivery to the Brain for the Treatment of Neurodegenerative Diseases.Frontiers in neuroscience · 2021Article
- Systematic use of synthetic 5'-UTR RNA structures to tune protein translation improves yield and quality of complex proteins in mammalian cell factories.Nucleic acids research · 2020Article
- A modular degron library for synthetic circuits in mammalian cells.Nature communications · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Comprehensive de novo-design of complex mammalian promoters is restricted by unpredictable combinatorial interactions between constituent transcription factor regulatory elements (TFREs). In this study, we show that modular binding sites that do not function cooperatively can be identified by analyzing host cell transcription factor expression profiles, and subsequently testing cognate TFRE activities in varying homotypic and heterotypic promoter architectures. TFREs that displayed position-insensitive, additive function within a specific expression context could be rationally combined together in silico to create promoters with highly predictable activities. As TFRE order and spacing did not affect the performance of these TFRE-combinations, compositions could be specifically arranged to preclude the formation of undesirable sequence features. This facilitated simple in silico-design of promoters with context-required, user-defined functionalities. To demonstrate this, we de novo-created promoters for biopharmaceutical production in CHO cells that exhibited precisely designed activity dynamics and long-term expression-stability, without causing observable retroactive effects on cellular performance. The design process described can be utilized for applications requiring context-responsive, customizable promoter function, particularly where co-expression of synthetic TFs is not suitable. Although the synthetic promoter structure utilized does not closely resemble native mammalian architectures, our findings also provide additional support for a flexible billboard model of promoter regulation.
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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.