期刊
ISCIENCE
卷 24, 期 6, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.isci.2021.102685
关键词
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资金
- Strategic Priority Research Program of Chinese Academy of Sciences [XDB 32060200]
- Shanghai Municipal Science and Technology Major Project [2018SHZDZX05]
- National Natural Science Foundation of China [31861143032]
- National Key Research and Development Program of China [2020YFA0112703]
This study demonstrates that co-infusion of the clinical anti-cancer drug doxorubicin can significantly enhance rAAV-mediated transgene expression, with effects observed across different mammalian species without detectable cytotoxicity.
Rapid and efficient gene transduction via recombinant adeno-associated viruses (rAAVs) is highly desirable across many basic and clinical research domains. Here, we report that vector co-infusion with doxorubicin, a clinical anti-cancer drug, markedly enhanced rAAV-mediated transgene expression in the cerebral cortex across mammalian species (cat, mouse, and macaque), acting throughout the time period examined and detectable at just three days after transfection. This enhancement showed serotype generality, being common to all rAAV sero-types tested (2, 8, 9, and PHP.eB) and was observed both locally and at remote locations consistent with doxorubicin undergoing retrograde axonal transport. All these effects were observed at doses matching human blood plasma levels in clinical therapy and lacked detectable cytotoxicity as assessed by cell morphology, activity, apoptosis, and behavioral testing. Altogether, this study identifies an effective means to improve the capability and scope of in vivo rAAV applications, amplifying cell transduction at doxorubicin concentrations paralleling medical practice.
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