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TANNylated-AAV for Enhanced Gene Delivery
Zheng Rong LAU,Ginah HAN,Jae-Hyung JANG 한국생물공학회 2021 한국생물공학회 학술대회 Vol.2021 No.4
Adeno-associated virus (AAV) has received tremendous attention for developments in gene therapy applications, leading to several approvals of AAV-based gene therapy products such as Glybera, Zolgensma, and Luxturna. However, much can still be done in optimizing the efficacy of AAV as a delivery vehicle for gene therapy. Among the many drawbacks of AAV as a delivery vector, the problem of its relatively low genome packaging capacity of only about 4.7 kb is especially detrimental, resulting in cases of which transgene need to be fragmented and packaged separately prior to administration. Herein, we demonstrate that through rather simple tannic acid treatment onto AAV to form tannic acid-treated AAV (namely TANNylated-AAV), the transduction efficiency is enhanced. Tannic acid is found to have high affinity to proline-rich extracellular matrices (ECM) and collagens, which leads us to hypothesize that TANNylated-AAV can allow for enhanced targeted delivery. We utilized hypoxic ischemic (HIE) brain injury mouse model to observe enhanced AAV transduction towards ECM-rich reactive astrocytes populated glial scar region of infarct area.