Researchers have introduced a new technology known as minimal versatile genetic perturbation technology (mvGPT). This breakthrough allows for the precise editing of genes, as well as the simultaneous activation and repression of gene expression. This innovative approach holds significant promise for treating genetic disorders and advancing our understanding of DNA functionality.
Groundbreaking innovations often result from reimagining existing technologies. For example, the iPhone integrated the functionalities of a phone, web browser, and camera among other devices.
Similarly, gene editing has evolved. Instead of relying on separate tools for gene modifications and expression regulation, researchers now combine these functions into one tool, enabling the simultaneous and independent treatment of various genetic conditions within the same cell.
Integrating Gene Editing with Regulation
A recent study published in Nature Communications by scientists at the Center for Precision Engineering for Health (CPE4H) at the University of Pennsylvania School of Engineering and Applied Science (Penn Engineering) introduces the minimal versatile genetic perturbation technology (mvGPT).
This technology can accurately edit genes, enhance gene expression, and suppress gene activity concurrently, paving the way for innovative treatments for genetic diseases and deeper insights into the workings of our DNA.
“Not all genetic disorders stem solely from mistakes in the genetic code,” explains Sherry Gao, Presidential Penn Compact Associate Professor in Chemical and Biomolecular Engineering (CBE) and Bioengineering (BE), and the lead author of the paper. “In some situations, diseases with a genetic basis—like type I diabetes—are influenced by the levels of gene expression.”
One Device with Numerous Capabilities
Previously, addressing several unrelated genetic issues at the same time—such as editing one gene while suppressing another—required multiple distinct tools. “Our goal was to create a unified platform that could efficiently modify DNA and regulate gene expression up or down,” states Tyler Daniel, a doctoral candidate in Gao’s lab and a co-first author of the publication.
The system combines an advanced “Prime Editor,” which modifies DNA sequences, with established methods for increasing and decreasing gene expression. “All these functions operate independently from one another,” notes Daniel. “They can occur simultaneously without affecting each other.”
“This degree of accuracy in editing DNA sequences along with gene expression was previously unattainable,” he adds. “Each function works autonomously. It’s as if we took a malfunctioning car, fixed its navigation system, turned up the stereo volume, and reduced the air conditioning—all at once.”
The Impact of Precise Editing
The research team tested mvGPT on human liver cells harboring a mutation linked to Wilson’s disease, successfully correcting the mutation while simultaneously enhancing a gene associated with type I diabetes treatment and suppressing another tied to transthyretin amyloidosis. In several trials, mvGPT performed all three functions with remarkable precision, showcasing its capacity to tackle multiple genetic conditions at once.
Since mvGPT occupies less space than would three separate tools, it is also more convenient to transport into cells. The researchers demonstrated that mvGPT can be successfully delivered using various methods, including mRNA strands and viral vectors designed for genetic editing.
“Having a single tool that can perform all these tasks simultaneously simplifies the process significantly, as it reduces the amount of machinery needed to be introduced into the cell,” says Gao.
Aiming for Greater Outcomes
With promising results in human cells, the researchers are preparing to evaluate mvGPT in animal models and explore its application against other genetically-related diseases, such as cardiovascular diseases. “The more advanced our tools, the more effective we can be in treating genetic disorders,” Gao concludes.
This research was conducted at the University of Pennsylvania School of Engineering and Applied Science, supported by the National Science Foundation (CBET-2143626) and the National Institutes of Health (HL157714).
Additional co-authors include co-first authors Qichen Yuan and Hongzhi Zeng from Rice University; Emmanuel C. Osikpa, Qiaochu Yang, Advaith Peddi, Liliana M. Abramson, and Boyang Zhang, also from Rice University; along with Qingzhuo Liu, Yongjie Yang, and Yong Xu from Baylor College of Medicine.