http://english.cas.cn/newsroom/research_news/life/202512/t20251229_1143167.shtml
LU Zhonghua’s team from the CAS Shenzhen Institute of Advanced Technology and collaborators from Peking University First Hospital, have developed Adeno-associated viruses (AAVs) with translocation LINKage (AAVLINK), which harnesses Cre/lox-mediated intermolecular DNA recombination to enable in vivo reassembly of large genes.
AAVLINK allows flexible gene segmentation design, achieves high-efficiency full-length gene reconstitution, and markedly reduces the production of aberrant truncated proteins compared with conventional approaches.
Using animal models, the researchers found that AAVLINK enabled robust expression of full-length Shank3 and significantly rescued autism-like behavioral phenotypes in Shank3-deficient mice, and the delivery of the large epilepsy-associated gene SCN1A using AAVLINK restored gene expression and alleviated seizure phenotypes in mutant mice. The findings provide strong evidence that AAVLINK supported functional delivery of large therapeutic genes in the nervous system.
Utilizing AAVLINK strategy, the researchers constructed a vector bank covering 193 large genes associated with inherited disorders including autism and epilepsy. They validated the gene reconstitution capacity of all constructs. Also, this vector bank comprised five CRISPR-based genetic tools, offering insights into the wide application of AAVLINK.
