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基因编辑进入“大规模重排时代”,桥重组酶:改写生命天书的“神笔”
Ke Ji Ri Bao· 2025-09-30 07:55
Core Insights - A revolutionary shift in gene editing technology is occurring, moving from simple corrections to comprehensive genomic restructuring, as demonstrated by the latest breakthroughs from the Arc Institute [1][2][3] Gene Editing Evolution - Traditional gene editing tools like CRISPR-Cas9 have been effective for precise corrections but struggle with complex diseases caused by large genomic rearrangements [2][3] - The limitations of existing technologies include their inability to efficiently handle large segments of DNA and the potential for off-target effects and safety risks [3] New Technology: Bridge Recombinase - The newly developed bridge recombinase technology allows for programmable insertions, deletions, and flips of genomic regions up to millions of base pairs, enabling large-scale genomic rearrangements [3][4] - This technology utilizes bridge RNA, which can simultaneously bind to two different DNA sites, facilitating complex genomic operations that were previously challenging with CRISPR [4] Clinical Applications and Potential - Initial experiments using bridge recombinase show promise in treating Friedrich's ataxia by successfully removing over 80% of the expanded GAA sequence responsible for the disease [5] - The technology simplifies the delivery process by requiring only RNA, reducing treatment complexity and risk, and has demonstrated broad applicability in existing therapies for conditions like sickle cell anemia [5] Future Prospects - The bridge recombinase technology holds potential for treating various genetic disorders, cancers, and applications in synthetic biology and agriculture [6] - Ongoing efforts are focused on applying this technology to stem cells and immune cells to develop more powerful variants for larger genomic segments [6]