Chinese researchers have introduced a genome editing platform capable of rewriting DNA at an unprecedented scale, from thousands of base pairs up to entire chromosomes.
Developed at the Chinese Academy of Sciences, the Programmable Chromosome Engineering (PCE) and RePCE systems promise leaps in crop breeding, medical research, and synthetic biology.
The work, published in Cell, builds on decades of recombinase-based editing by removing long-standing limitations and integrating artificial intelligence to tune the underlying enzymes for speed and accuracy at massive scales.
Breaking past Cre-Lox limits
Reversible reactions, complex protein architecture, and unwanted DNA scars at edit sites hampered the older Cre-Lox approach. These issues limited stability, precision, and scalability for chromosome engineering.
The PCE team created asymmetric Lox sites to cut reversal rates by more than 90 percent while retaining high efficiency. They coupled this with AI-driven protein design, generating a Cre recombinase variant 3.5 times faster than the original.
Did you know?
The Cre-Lox recombination system, first developed in the 1980s, originally came from a P1 bacteriophage and has since been central to genetic engineering in plants, animals, and microorganisms.
Precision without scars
The researchers also developed Re-pegRNA, a method to restore the original DNA sequence at edit junctions. This scarless approach eliminates residual sites, enabling cleaner and more predictable outcomes for large-scale edits.
The combination of these upgrades allows scientists to plan intricate, multi-megabase modifications with high fidelity and an engineering scale previously out of reach in plant or animal cells.
Editing on a massive scale
In demonstrated tests, the team inserted DNA fragments up to 18.8 kilobases, replaced 5-kilobase stretches, performed inversions up to 12 megabases, deleted 4-megabase blocks, and relocated entire chromosomes.
A proof-of-concept trial produced herbicide-resistant rice by inverting a 315-kilobase segment, showcasing potential for targeted agricultural improvement.
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Applications in crops and medicine
Beyond agriculture, the technology could accelerate therapeutic strategies that require reshaping genome structure, such as removing large defective regions or integrating complex genetic circuitry in human cells.
Synthetic biology stands to benefit from PCE’s capacity for artificial chromosome creation, unlocking designs for organisms with entirely novel metabolic or developmental traits.
How it compares to CRISPR
CRISPR remains efficient for single-gene edits or small insertions but is less suited for structural genome overhauls. PCE complements CRISPR by enabling chromosomal-scale changes, allowing researchers to modify genetic architecture as well as content.
Looking ahead
Experts expect early adoption in experimental crop programs and model organism research, with medical applications following rigorous safety and delivery validation.
By expanding the editable canvas from genes to chromosomes, PCE could help define the next era in genetic engineering, one where precision and scale work hand-in-hand to reshape biology.
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