CRISPR-mediated precise large fragment insertion in zygotes enables rapid generation of humanized immunoglobulin heavy-chain mice.

CRISPR enables precise insertion of 155-kb human immunoglobulin sequences into mouse zygotes, producing humanized mice within 8 weeks.

• Why it matters: This advances the ability to rapidly generate humanized models with large genomic modifications, addressing limitations of current CRISPR methods that are restricted to small edits.
• What they did: The team deleted a 2.4-Mb mouse IgH locus and inserted a bacterial artificial chromosome containing human V H segments using a CRISPR-guided approach, achieving stable, single-copy integration.
• The result: The resulting mice expressed human V H segments that recombined and functioned normally, enabling human-like antibody responses and rapid model development for immunological research.