The Programmable Era of Life

The convergence of genome editing, directed evolution, and de novo protein design is moving the life sciences from reading and rewriting DNA toward designing it. Crop improvement is following the same path, shifting from breeding that relies on random variation toward a predictable, programmable era of rational design. Centered on the precise improvement of crop genomes, our work pursues original innovation along three fronts.

In precision genome editing, we uncovered how type V CRISPR nucleases evolved from transposon-encoded TnpB, showing that the functional splitting of a guide RNA drove the emergence of CRISPR systems. On this basis we created TranC, a compact editor independent of Cas9 with full, self-owned intellectual property. We also developed PrimeRoot for targeted large-fragment DNA insertion in plants and clarified a guide-RNA-independent off-target mechanism of base editing, substantially improving precision and controllability.

In AI-guided protein design and chromosome engineering, we established a structure-driven method for protein clustering and AiCE, an AI-guided zero-shot approach to protein directed evolution that efficiently designed a series of novel deaminases and other editing components. By engineering recombinases, we further built Precise Chromosome Editing (PCE), advancing from single-base modification to chromosome-scale restructuring. In in planta directed evolution and programmable immunity, we developed GRAPE, a geminivirus replicon-assisted system that evolves plant proteins within their native cellular context, and a platform for Synthetic Plant Immune Receptors (SPIRs) that shifts disease resistance from discovery to design. Applied to coupling powdery mildew resistance with high yield in wheat and to herbicide-tolerant rice, among other elite germplasm, these tools mark the entry of precision crop breeding into a design-driven, programmable era of life.