中国比较医学杂志2026，Vol.36Issue(14)：13-23,11.DOI:10.3969/j.issn.1671-7856.2026.14.002
不同AAV突变衣壳在食蟹猴脑的转导效果分析
Analysis of AAV capsid variant-mediated transduction capability in the macaque brain
摘要
Abstract
Objective To systematically evaluate the neuronal transduction efficiency of adeno-associated virus(AAV)capsid variants,including AAV-PHP.B and AAV-PHP.eB,in the brain of cynomolgus monkeys(Macaca fascicularis),and to analyze the effects of different injection doses and routes on whole-brain infection.Methods Recombinant AAVs carrying the hSyn-EYFP expression cassette packaged into AAV9,AAV-PHP.B,and AAV-PHP.eB capsids were administered to cynomolgus monkeys through different routes(intracerebroventricular injection(ICV),intracisternal magna injection(ICM),and intravenous injection(IV))and at different doses.After 6 weeks of transgene expression,the animals were perfused,and brain tissues were collected for cryosectioning and immunofluorescence staining.The ratio of EYFP and NeuN co-labeled cells to the total NeuN-positive cells in regions including the prefrontal cortex,caudate/putamen nucleus,hippocampus,and thalamus was quantified to assess neuronal transduction efficiency.Results Following ICV injection,low-dose AAV-PHP.B(1×1013 vg/kg)demonstrated significantly higher neuronal transduction efficiency than AAV9 in the prefrontal cortex(8.4％vs.1.2％,P<0.000 1)and caudate/putamen nucleus(6.3％vs.0.5％,P<0.000 1).Increasing the AAV-PHP.B dose to 5×1013 vg/kg further enhanced its efficiency in the caudate/putamen nucleus(P<0.000 1).Combined ICV and ICM injection synergistically enhanced the whole-brain transduction of AAV-PHP.B,particularly in the prefrontal cortex(14.7％)and thalamus(2.6％).When delivered using the combined route,AAV-PHP.eB showed significantly superior transduction efficiency in deep brain structures such as the hippocampus and thalamus compared with AAV-PHP.B(P<0.01).In contrast,intravenous injection of AAV-PHP.eB failed to achieve efficient transduction(<1％)in any brain region examined.Conclusions The AAV-PHP.B and AAV-PHP.eB capsids exhibited superior transduction capabilities in the cynomolgus monkey brain compared with AAV9.Combined ICV and ICM injection represents a highly effective approach for achieving widespread neuronal transduction throughout the brain.This study provides crucial experimental evidence for selecting appropriate AAV delivery tools and optimizing administration protocols for non-human primate studies and future clinical translation.关键词
腺相关病毒/脑部转导/注射方式/突变衣壳/食蟹猴Key words
adeno-associated virus/brain transduction/injection routes/capsid variants/cynomolgus monkey分类
医药卫生引用本文复制引用
秦一帆,陈晔菲,洪泽璇,路中华,张誉竞,严世荣..不同AAV突变衣壳在食蟹猴脑的转导效果分析[J].中国比较医学杂志,2026,36(14):13-23,11.基金项目
国家自然科学基金(32400927) （32400927）
深圳市医学研究专项资金项目(B2402029). （B2402029）
