1103-Synthetic Rewriting of the IGH Locus

Researchers have successfully developed SynIgh, a synthetic human immunoglobulin heavy chain locus designed de novo to explore and expand antibody diversity. This modular construct was engineered using genes from global human populations and integrated into a mouse model to demonstrate functional V(D)J recombination. To overcome the structural instability of highly repetitive sequences, the team utilized a specialized DNA stabilizer during the assembly process in microbial hosts. A key feature of the project is the mSCRaMbLE system, which allows for programmable, inducible shuffling of the genomic locus in living cells. This synthetic rearrangement successfully bypassed natural structural constraints, significantly increasing the variety of recombination outcomes. Ultimately, this work provides a scalable framework for mammalian genome rewriting and deeper investigation into immune system architecture.

References:

• Fu Z H, Ma Y, Cheng S, et al. Synthetic rewriting of the IGH locus[J]. Cell Genomics, 2026.