Multiple Input Sensing and Signal Integration Using a Split Cas12a System
| Autor: | Laine E. Goudy, Hannah R. Kempton, Lei S. Qi, Kasey S. Love |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Transcriptional Activation
Cell engineering CRISPR-Associated Proteins Breast Neoplasms Biology Signal 03 medical and health sciences Synthetic biology 0302 clinical medicine Cell Line Tumor Humans Molecular Biology Cell Engineering 030304 developmental biology 0303 health sciences business.industry fungi Cell Biology Multiple input HEK293 Cells Coupling (computer programming) Proof of concept Logic gate Female CRISPR-Cas Systems business Dimerization 030217 neurology & neurosurgery AND gate Computer hardware |
| Zdroj: | Molecular cell. 78(1) |
| ISSN: | 1097-4164 |
| Popis: | The ability to integrate biological signals and execute a functional response when appropriate is critical for sophisticated cell engineering using synthetic biology. Although the CRISPR-Cas system has been harnessed for synthetic manipulation of the genome, it has not been fully utilized for complex environmental signal sensing, integration, and actuation. Here, we develop a split dCas12a platform and show that it allows for the construction of multi-input, multi-output logic circuits in mammalian cells. The system is highly programmable and can generate expandable AND gates with two, three, and four inputs. It can also incorporate NOT logic by using anti-CRISPR proteins as an OFF switch. By coupling the split dCas12a design to multiple tumor-relevant promoters, we provide a proof of concept that the system can implement logic gating to specifically detect breast cancer cells and execute therapeutic immunomodulatory responses. |
| Databáze: | OpenAIRE |
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