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Mol. Ther., Available online 7 January 2022 | https://doi.org/10.1016/j.ymthe.2022.01.010 Non-invasive administration of AAV to target lung parenchymal cells and develop SARS-CoV-2-susceptible mice

Myeon-Sik Yang^1,8, Min-Jung Park^2,3,8, Junhyeong Lee^2,3,8, Byungkwan Oh¹, Kyung Won Kang⁴, Yeonhwa Kim⁵, Sang-Myeong Lee⁵, Je-Oh Lim³, Tae-Yang Jung³, Jong-Hwan Park^3,6, Seok-Chan Park¹, Yun-Sook Lim⁷, Soon B. Hwang⁷, Kwang-Soo Lyoo⁷, Dong-il Kim^2,3,*, Bumseok Kim^1,7,*

¹Biosafety Research Institute and Laboratory of Veterinary Pathology, College of Veterinary Medicine, Jeonbuk National University, Iksan 54596, Korea
²Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Korea
³College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju 61186, Korea
⁴Division of Biotechnology, College of Environmental and Bioresources, Jeonbuk National University, Iksan 54596, Korea
⁵College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Korea
⁶Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Korea
⁷Korea Zoonosis Research Institute, Jeonbuk National University, Iksan 54531, Korea
⁸These authors contributed equally

^*Corresponding author

Abstract

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.

Keywords : AAV, SARS-CoV-2, hACE2, lung targeting, AT1, AT2, AAV2/8, intratracheal injection

논문정보

형식Research article
게재일2022년 01월 (BRIC 등록일 2022-02-18)
연구진국내 연구진
분야 생명과학 > 수의학

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