Synthetic tools conduct messages from station to station in DNA

Rice University researchers have demonstrated that CRISPR-Cas9, increasingly famous as a gene-editing tool, can be employed in powerful additional ways in human cells.

A team led by Rice bioengineer Isaac Hilton and graduate student Kaiyuan Wang used deactivated Cas9 (dCas9) proteins to target key segments of the human genome and synthetically trigger the transcription of human genes.

By using dCas9 to recruit proteins that can naturally turn genes on, the Rice team was able to reveal important details about human promoters and enhancers — the pieces of our DNA that coordinate when, and to what extent, our genes are turned on — which in turn controls the behaviors of our cells.

“We’re using these synthetic biology tools to improve the ability to engineer gene expression and program human cells, and consequently to better understand how our genes work naturally,” Hilton said. “These types of studies are important because in the long run this knowledge and these technical capabilities can enable better gene and cell therapies and biotechnologies.”

Hilton said the study in Nucleic Acids Research highlights the growing potential of CRISPR-Cas9-based tools for synthetic gene control and cellular engineering. The team’s strategy also demonstrates the power of dCas9 to influence and understand the epigenetic factors that animate the human genome.

“Only around 2% of our genome contains protein-coding genes, and the remaining 98% is so-called noncoding DNA,” Hilton said. “Enhancers and promoters are key parts of our noncoding genomes and, although the vast majority of these elements do not make conventional genes, there is fascinating genetic variation in noncoding DNA. This variation gives us the magnificent diversity that enables our species to be both amazing and adaptable.

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