The human genome holds about three billion base pairs within each cell. Although tools like Crispr have revolutionized the editing of single genes and individual nucleic acid bases, researchers have found it far difficult to accurately alter larger stretches of DNA involving thousands or millions of bases.
Now, a team of Chinese scientists led by Gao Caixia, principal investigator at Chinese Academy of Sciences’ Institute of Genetics and Developmental Biology, has cracked a decades-old challenge in genetic engineering by creating a tool that can precisely manipulate millions of DNA base pairs—the fundamental units of life’s code.
The advancement has been described as very significant progress by professor Yin Hao, a gene-editing expert at Wuhan University’s medical research institute, who was not part of the research. Speaking to the South China Morning Post (SCMP), he added that the development could lay the groundwork for transformative breakthroughs in biomedicine and agriculture.
Major leap in plant genome editing with PCE systems
As part of their study, the scientists enhanced a decade-old gene-editing method, making it far easier to use and significantly more efficient. Published in the peer-reviewed journal Cell, the paper explains how the new programmable chromosome engineering (PCE) systems can precisely modify large DNA fragments, involving millions of bases, in higher organisms, particularly plants.
This breakthrough could reshape research in fast-growing fields like agricultural seed cultivation and synthetic biology. The Beijing branch of the Chinese Academy of Sciences stated that by enabling manipulation of genomic structural variation, the technology will open up new avenues for improving crop traits and treating genetic diseases. It may also speed progress toward artificial chromosomes, which hold vast potential for next-generation applications in synthetic biology, SCMP reported.
Professor Yin explained that the journey started with Cre-Lox, a key enzyme in biomedicine widely used to insert, invert, or replace large DNA segments and perform other genetic edits. However, since its discovery in the 1980s, Cre-Lox’s limitations have discouraged researchers. Its efficiency drops significantly as the size of the targeted DNA fragment grows, and the enzyme often leaves behind “scars,” complicating further genetic work.
Advances in genome editing promise more permanent DNA changes
The Wuhan-based scientist noted that because the edited DNA sequences could be reversed, the changes were often temporary despite extensive efforts to achieve specific genetic modifications.
This is where Gao and her team stepped in. Focusing on genome editing technologies, especially in agriculture—they redesigned and optimized editing strategies to overcome these challenges, resulting in new methods that significantly advance the field.
This new PCE technique offers precise manipulation of DNA fragments with efficiency more than 3.5 times that of the original enzyme editor, while eliminating scarring and minimizing the risk of reversal.
While scientists previously needed to edit 1,000 seeds to find just one with the desired traits, the enhanced tool now cuts that number down to only 100, significantly easing workload for researchers. Furthermore, it is expected that PCE systems will eventually replace existing Cre-Lox systems in laboratories worldwide, introducing greater efficiency to both medical research and agricultural engineering.