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Non-invasive administration of AAV to target lung parenchymal cells and develop SARS-CoV-2-susceptible mice.
Yang, Myeon-Sik; Park, Min-Jung; Lee, Junhyeong; Oh, Byungkwan; Kang, Kyung Won; Kim, Yeonhwa; Lee, Sang-Myeong; Lim, Je-Oh; Jung, Tae-Yang; Park, Jong-Hwan; Park, Seok-Chan; Lim, Yun-Sook; Hwang, Soon B; Lyoo, Kwang-Soo; Kim, Dong-Il; Kim, Bumseok.
  • Yang MS; Biosafety Research Institute and Laboratory of Veterinary Pathology, College of Veterinary Medicine, Jeonbuk National University, Iksan 54596, Korea.
  • Park MJ; Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Korea; College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju 61186, Korea.
  • Lee J; Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Korea; College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju 61186, Korea.
  • Oh B; Biosafety Research Institute and Laboratory of Veterinary Pathology, College of Veterinary Medicine, Jeonbuk National University, Iksan 54596, Korea.
  • Kang KW; Division of Biotechnology, College of Environmental and Bioresources, Jeonbuk National University, Iksan 54596, Korea.
  • Kim Y; College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Korea.
  • Lee SM; College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Korea.
  • Lim JO; College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju 61186, Korea.
  • Jung TY; College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju 61186, Korea.
  • Park JH; College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju 61186, Korea; Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Korea.
  • Park SC; Biosafety Research Institute and Laboratory of Veterinary Pathology, College of Veterinary Medicine, Jeonbuk National University, Iksan 54596, Korea.
  • Lim YS; Korea Zoonosis Research Institute, Jeonbuk National University, Iksan 54531, Korea.
  • Hwang SB; Korea Zoonosis Research Institute, Jeonbuk National University, Iksan 54531, Korea.
  • Lyoo KS; Korea Zoonosis Research Institute, Jeonbuk National University, Iksan 54531, Korea.
  • Kim DI; Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Korea; College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju 61186, Korea. Electronic address: kimdi@chonnam.ac.kr.
  • Kim B; Biosafety Research Institute and Laboratory of Veterinary Pathology, College of Veterinary Medicine, Jeonbuk National University, Iksan 54596, Korea; Korea Zoonosis Research Institute, Jeonbuk National University, Iksan 54531, Korea. Electronic address: bskims@jbnu.ac.kr.
Mol Ther ; 30(5): 1994-2004, 2022 05 04.
Article in English | MEDLINE | ID: covidwho-1612107
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Limits: Animals Language: English Journal: Mol Ther Journal subject: Molecular Biology / Therapeutics Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Limits: Animals Language: English Journal: Mol Ther Journal subject: Molecular Biology / Therapeutics Year: 2022 Document Type: Article