Breakthroughs in gene editing and expression control with mvGPT

Influential inventions often combine existing tools in new ways. The iPhone, for instance, amalgamated the telephone, web browser and camera, among many other devices.

The same is now possible in gene editing. Rather than employ separate tools for editing genes and regulating their expression, these distinct goals can now be combined into a single tool that can simultaneously and independently address different genetic diseases in the same cell.

In a new paper in Nature Communications, researchers in the Center for Precision Engineering for Health (CPE4H) at the School of Engineering and Applied Science describe their findings: minimal versatile genetic perturbation technology (mvGPT).

Capable of precisely editing genes, activating gene expression and repressing genes all at the same time, the technology opens new doors to treating genetic diseases and investigating the fundamental mechanisms of how our DNA functions.

"Not all genetic diseases are solely caused by errors in the genetic code itself," says Sherry Gao, Presidential Penn Compact Associate Professor in Chemical and Biomolecular Engineering and in Bioengineering and the paper's senior author. "In some cases, diseases with genetic components-like type I diabetes-are due to how much or little certain genes are expressed."

In the past, addressing multiple, unrelated genetic abnormalities at once-for example, by editing one gene and suppressing another-would have required multiple distinct tools. "We wanted to build a single platform that could precisely and efficiently edit DNA as well as upregulate and downregulate gene expression," says Tyler Daniel, a doctoral student in the Gao Lab and one of the paper's co-first authors.

The team tested mvGPT on human liver cells with a mutation causing Wilson's disease, successfully editing out the mutation while also upregulating a gene linked to type I diabetes treatment and suppressing another associated with transthyretin amyloidosis.

In multiple tests, mvGPT achieved all three tasks with high precision, demonstrating its ability to target multiple genetic conditions simultaneously.

Read more at Penn Engineering Today.