Composable mammalian elements of transcription (COMET) toolkit for bioengineers
- 技术优势
- Modular components increase versatility Components are readily tunable
- 详细技术说明
- A toolkit of engineered gene expression components that can be combined and fine-tuned to develop sophisticated and customized cellular functions. #therapeutics #cellsignaling #healthcare #researchtool #gene
- *Abstract
-
BACKGROUND
Synthetic biology is a rapidly evolving field that combines the principles of biology and engineering to design and create artificial biological building blocks for applications in industry and research. One such example includes cell-based therapeutics, in which the design of mammalian cells using synthetic receptors and signal transduction systems can be engineered. To date, however, the tools available for composing such biological systems are limited in number and fine-tuning the performance of these individual biological components is quite challenging.
ABSTRACT
Northwestern inventors have developed the Composable Mammalian Elements of Transcription (COMET) toolkit. COMET is comprised of a series of engineered building blocks for controlling gene expression, including DNA sequences and associated synthetic regulatory proteins. By engineering specific sequences into the DNA, selective protein binding sites may be promoted. Binding of the protein to its complementary DNA sequence then induces expression of a downstream reporter gene. In a therapeutic setting, for instance, this reporter gene could be replaced with a gene for a protein known to fight cancer cells. Both the proteins and their associated DNA sequences are modular in design, enabling the ability to tune the quantitative performance of the system (i.e. how much of the downstream gene is expressed) and to vary the combination of elements. The versatility in building sophisticated and customized cellular functions is tremendous. In preliminary cellular studies, the researchers demonstrated the modular function of the building blocks by engineering a DNA sequence with binding sites for two proteins. For expression of a reporter gene to occur, both proteins must bind. Results showed that only when both proteins were present, robust gene activation was achieved. In another example, sequential gene expression was achieved by placing the activation of one regulatory protein under the control of a second. The COMET toolkit will have useful applications for controlling the gene expression in fundamental research, biotechnology, and medicine.
- *Inventors
- Joshua N. Leonard* Patrick Donahue
- *Publications
- In preparation
- 国家/地区
- 美国
