简单说明
Blood clotting works as a chain of proteins, each activating the next. In haemophilia one link is missing, so clots form too slowly and bleeding continues — into joints and muscles, and sometimes dangerously. Approved gene therapies already put a working copy of the missing gene into liver cells. The reason to try editing instead is that added copies can fade over time, particularly in children whose livers are still growing, while an edit at the gene's own address should last.
深入了解
Haemophilia A and B result from F8 and F9 mutations respectively, both X-linked. Approved AAV gene-addition therapies deliver functional transgenes to hepatocytes and have produced substantial factor expression, but episomal AAV genomes dilute with hepatocyte turnover — a particular limitation in paediatric patients — and pre-existing anti-AAV immunity excludes a significant fraction of patients. Targeted integration at a safe-harbour locus such as albumin, or in situ correction, aims for durability that survives cell division.
The durability argument
This is the clearest case where editing's advantage over gene addition is about time rather than capability. An AAV episome is not copied when a cell divides, so as the liver renews itself the therapeutic copies are diluted away. Integrating the sequence, or editing the endogenous gene, means every daughter cell inherits it. For a child who will live another seventy years, that difference is the whole argument.
Sources
- U.S. Food and Drug Administration
Approved cellular and gene therapy products ↗