ArticleNucleic acids research2013
Two- and three-input TALE-based AND logic computation in embryonic stem cells.
Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- Gene circuit-based sensors.Fundamental research · 2025Review
- Programmable trans-splicing riboregulators for complex cellular logic computation.Nature chemical biology · 2025Article
- Development of a new caged intein for multi-input conditional translation of synthetic mRNA.Scientific reports · 2024Article
- Combinatorial protein dimerization enables precise multi-input synthetic computations.Nature chemical biology · 2023Article
- Synthetic gene circuits for cell state detection and protein tuning in human pluripotent stem cells.Molecular systems biology · 2022Article
- Model-guided design of mammalian genetic programs.Science advances · 2021Article
- An expanded library of orthogonal split inteins enables modular multi-peptide assemblies.Nature communications · 2020Article
- Split-TALE: A TALE-Based Two-Component System for Synthetic Biology Applications in Planta.Plant physiology · 2019Article
- Polarized displacement by transcription activator-like effectors for regulatory circuits.Nature chemical biology · 2019Article
- Designing cell function: assembly of synthetic gene circuits for cell biology applications.Nature reviews. Molecular cell biology · 2018Review
- Transcription control engineering and applications in synthetic biology.Synthetic and systems biotechnology · 2017Review
- Exploiting the sequence diversity of TALE-like repeats to vary the strength of dTALE-promoter interactions.Synthetic biology (Oxford, England) · 2017Article
- Synthetic Biology Platform for Sensing and Integrating Endogenous Transcriptional Inputs in Mammalian Cells.Cell reports · 2016Article
- Engineering Gene Circuits for Mammalian Cell-Based Applications.Cold Spring Harbor perspectives in biology · 2016Review
- Synthetic dual-input mammalian genetic circuits enable tunable and stringent transcription control by chemical and light.Nucleic acids research · 2016Article
- A transcription activator-like effector (TALE) induction system mediated by proteolysis.Nature chemical biology · 2016Article
- Locked and proteolysis-based transcription activator-like effector (TALE) regulation.Nucleic acids research · 2016Article
- Editing the epigenome: technologies for programmable transcription and epigenetic modulation.Nature methods · 2016Review
- Designer cell signal processing circuits for biotechnology.New biotechnology · 2015Review
- Reconfigurable hybrid interface for molecular marker diagnostics and in-situ reporting.Biosensors & bioelectronics · 2015Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Biological computing circuits can enhance our ability to control cellular functions and have potential applications in tissue engineering and medical treatments. Transcriptional activator-like effectors (TALEs) represent attractive components of synthetic gene regulatory circuits, as they can be designed de novo to target a given DNA sequence. We here demonstrate that TALEs can perform Boolean logic computation in mammalian cells. Using a split-intein protein-splicing strategy, we show that a functional TALE can be reconstituted from two inactive parts, thus generating two-input AND logic computation. We further demonstrate three-piece intein splicing in mammalian cells and use it to perform three-input AND computation. Using methods for random as well as targeted insertion of these relatively large genetic circuits, we show that TALE-based logic circuits are functional when integrated into the genome of mouse embryonic stem cells. Comparing construct variants in the same genomic context, we modulated the strength of the TALE-responsive promoter to improve the output of these circuits. Our work establishes split TALEs as a tool for building logic computation with the potential of controlling expression of endogenous genes or transgenes in response to a combination of cellular signals.
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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.