Non-invasive administration of AAV to target lung parenchymal cells and develop SARS-CoV-2-susceptible mice.

Adeno-associated virus (AAV)-mediated gene delivery holds great promise for gene therapy. However, the non-invasive delivery of AAV for lung tissues has not been adequately established. Here, we revealed that the intratracheal administration of an appropriate amount of AAV2/8 predominantly targets lung tissue. AAV-mediated gene delivery that we used in this study induced the expression of the desired protein in lung parenchymal cells, including alveolar type II cells. We harnessed the technique to develop severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-susceptible mice. Three kinds of immune function-relevant gene knockout (KO) mice were transduced with AAV encoding human angiotensin-converting enzyme 2 (hACE2) and then injected with SARS-CoV-2. Among these mice, type I interferon receptor (IFNAR) KO mice showed increased viral titer in the lungs compared to that in the other KO mice. Moreover, nucleocapsid protein of SARS-CoV-2 and multiple lesions in the trachea and lung were observed in AAV-hACE2-transduced, SARS-CoV-2-infected IFNAR KO mice, indicating the involvement of type I interferon signaling in the protection of SARS-CoV-2. In this study, we demonstrate the ease and rapidness of the intratracheal administration of AAV for targeting lung tissue in mice, and this can be used to study diverse pulmonary diseases. Copyright © 2022 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Citation

Myeon-Sik Yang, Min-Jung Park, Junhyeong Lee, Byungkwan Oh, Kyung Won Kang, Yeonhwa Kim, Sang-Myeong Lee, Je-Oh Lim, Tae-Yang Jung, Jong-Hwan Park, Seok-Chan Park, Yun-Sook Lim, Soon B Hwang, Kwang-Soo Lyoo, Dong-Il Kim, Bumseok Kim. Non-invasive administration of AAV to target lung parenchymal cells and develop SARS-CoV-2-susceptible mice. Molecular therapy : the journal of the American Society of Gene Therapy. 2022 May 04;30(5):1994-2004

Mesh Tags

PMID: 35007757

search → result