A New Era of Gene Editing: One Tool to Edit, Activate, and Silence Genes at Once

This blog post serves to simplify this scholarly article: 

• "Orthogonal and multiplexable genetic perturbations with an engineered prime editor and a diverse RNA array" published in the Nature Communications Journal by Qichen Yuan and other authors

Imagine being able to fix a genetic mutation that causes disease, activates a protective gene, and silences a harmful one; all in the same cell, at the same time. That’s exactly what researchers have achieved with a new gene-editing system called mvGPT. This breakthrough represents a major leap forward in precision medicine, where one compact tool could correct complex genetic conditions that involve multiple genes.

What is the current technology look like?

Traditional gene-editing technologies, like CRISPR/Cas9, have transformed biology and medicine, but they still face major challenges. CRISPR works by cutting DNA, which relies on the cell’s natural repair systems to fix the damage. Unfortunately this process can lead to unintended mutations or even cell death, posing a serious risk in human cells. 

Later innovations, such as base editors, offered a safer approach by directly changing single DNA letters (or "nucleotides") without cutting both strands. However, base editors can only make simple point mutations and can’t handle more complex changes or control gene activity.

The new system introduced in this study; mvGPT (minimal versatile genetic perturbation technology) builds on a next-generation tool called prime editing. Prime editors can precisely insert, delete, or rewrite DNA sequences without creating dangerous breaks. What makes mvGPT revolutionary is that it combines prime editing with additional tools that can turn genes on or off at the same time. This allows for simultaneous and independent (orthogonal) control of multiple genes something no previous system could do efficiently. This breakthrough opens the door to more powerful research tools and safer, more flexible gene therapies that could one day transform how we treat genetic diseases.

Figure authored by writer

What were the researchers trying to understand?

Can scientists create a single, compact genetic tool that can edit genes, turn some on, and turn others off all at the same time safely and efficiently? 

The main question they asked was whether they could design a versatile system that does multiple genetic changes at once in a controlled way. This would make it possible to study or treat complex diseases that involve several genes interacting together, such as metabolic disorders, cancers, or neurological diseases. To measure how effective their system was, they used fluorescent reporter genes, which light up when certain genes are activated or silenced. This allowed them to visually confirm that mvGPT could perform editing, activation, and repression at the same time within the same cells. They also used RNA sequencing to analyze gene expression changes at the molecular level, confirming that the targeted genes behaved exactly as programmed.

In addition, they tested the system using both viral and non-viral delivery methods, showing that mvGPT could be introduced into human cells in several different ways, increasing its flexibility for research and potential therapeutic use. The platform’s design using smaller, modular components helped reduce the delivery size, making it easier to package into viral vectors like AAV (adeno-associated virus), viruses that transmit DNA or other bio-materials .

Their approach was focused on creating a compact, programmable system that can safely make multiple, precise genetic changes without cutting DNA strands; something older CRISPR-based methods couldn’t achieve without risking unwanted mutations.

What did they find? 

The results showed that mvGPT can perform three genetic actions at once: editing, activation, and repression. The optimized prime editor (PEAK) made precise DNA changes up to 69% more efficiently than older versions. The activation system could boost gene expression by a thousand times, while the RNA-based silencing system turned off the genes with over 90% efficiency. When combined, mvGPT was able to fix, turn on, and silence the different disease related genes in human cells all at once; something that no previous system could do so compactly or safely. 

What’s Next? 

The mvGPT system is still being tested but researchers plan to test mvGPT in animal models and primary human cells to confirm its safety and accuracy. They also plan to study how the system can be refined to further reduce off-target effects like unintended edits and improve delivery efficiency in different tissues. If successful, the mvGPT could become a core technology for treating complex diseases that involve multiple genes.

The development of mvGPT shows that the future of medicine is more than cutting DNA; it’s about communicating with it. With this system, scientists can explore diseases in new dimensions, safely and precisely, opening doors to therapies that once seemed impossible. 

Related Areas to research? 

• Prime Editing vs. CRISPR-Cas9 

• Multi-gene therapy development 

• AI-guided genome engineering 

• Ethical considerations in multiplexed editing