Researchers at the Arc Institute have developed programmable bridge recombinase systems capable of megabase-scale DNA rearrangements in human cells. This technology allows large-scale gene insertions, deletions, and inversions beyond the small precise edits currently possible with CRISPR. Bridge recombinases, naturally derived RNA-guided DNA enzymes, were optimized for human applications, achieving insertion efficiencies up to 20%. This paradigm-shifting advance could revolutionize genetic therapies by enabling complex genomic engineering at evolutionary scales, potentially yielding versatile treatments for genetic diseases.