Revolutionary Gene Editor Brings Precision DNA Insertion Closer to Reality.

A new gene-editing system named evoCAST is bringing scientists one step closer to a long-sought goal in gene therapy: precisely inserting complete genes into specific sites in the human genome without causing unintended genetic damage. Developed by researchers in the labs of Samuel Sternberg at Columbia University and David Liu at the Broad Institute of MIT and Harvard, evoCAST marks a significant advancement in the field of genetic medicine.

From the earliest days of gene therapy, researchers have grappled with how to safely and accurately introduce long DNA sequences into human cells. Traditional methods like CRISPR-Cas9 excel at making small edits, while viral vectors, though capable of inserting entire genes, tend to act unpredictably and can provoke immune responses. evoCAST offers a potential solution—combining the precision of CRISPR-based systems with the ability to install large genetic payloads.

The new tool, described in detail in a Science publication, harnesses complex bacterial enzymes to guide the insertion of complete genes—or even multiple genes—into defined locations within the human genome. This system shows editing efficiencies high enough to make it practical for gene therapy, especially in diseases such as cystic fibrosis and hemophilia, where a wide variety of mutations in a single gene can cause illness.

cystic fibrosis, for instance, hundreds or even thousands of different mutations in the CFTR gene can lead to disease,” explained Sternberg. “Rather than developing countless gene-editing treatments tailored to each mutation, evoCAST could allow us to insert a full, functional copy of the gene—bypassing the mutation altogether.”

Beyond single-gene disorders, evoCAST holds promise for a wide range of applications, including the manufacturing of CAR T-cell therapies for cancer and creating genetically engineered cells and organisms for research.

The technology traces its roots to bacterial "jumping genes", also known as transposons, which naturally move within the genome to foster diversity. Sternberg’s team discovered a family of enzymes called CRISPR-associated transposases (CASTs) that can insert large segments of DNA without cutting the host chromosome—minimizing the risk of harmful side effects.

However, adapting this bacterial mechanism to human cells proved difficult. Graduate student George Lampe led the initial development, but early results showed poor efficiency. To improve the system, the team collaborated with Liu, who developed a technique called PACE (phage-assisted continuous evolution). This method rapidly evolves proteins through hundreds of generations, dramatically enhancing their performance.

Lampe’s work brought evoCAST to the point where it could enter PACE, and Liu’s graduate students Isaac Witte and Simon Eitzinger used the method to optimize the system. The evolved version of evoCAST achieved editing rates of 30% to 40%—a substantial improvement over the original system’s capabilities.

Although evoCAST has now reached an efficiency suitable for many therapeutic uses, work is ongoing to further enhance its accuracy and functionality. The research teams are also beginning to test the system in more advanced biological models to assess its real-world applicability.

One significant hurdle remains: delivery. “Even with a tool as promising as evoCAST, the big question is how to deliver it—and its genetic cargo—precisely to the right cells or tissues,” said Sternberg. This challenge is not unique to evoCAST but is shared across the field of gene editing.

Despite this, the development of evoCAST represents a major leap forward, offering hope for more robust and universal gene therapies in the near future.

Source:https://phys.org/news/2025-05-advanced-gene-editor-enables-precise.html

This is non-financial/medical advice and made using AI so could be wrong.