한빛사논문
- 조회654
Jeonghwan Kim 1, Antony Jozic 1, Anindit Mukherjee 1, Dylan Nelson 1 2, Kevin Chiem 3, Md Siddiqur Rahman Khan 3, Jordi B Torrelles 3, Luis Martinez-Sobrido 3, Gaurav Sahay 1 4 5
1Department of Pharmaceutical Sciences, College of Pharmacy, Robertson Life Sciences Building, Oregon State University, Portland, OR, 97201, USA.
2High-Throughput Screening Services Laboratory, College of Pharmacy, Oregon State University, Corvallis, OR, 97331, USA.
3Disease Prevention and Intervention, and Population Health Programs, Texas Biomedical Research Institute, San Antonio, TX, 78227, USA.
4Department of Biomedical Engineering, Robertson Life Sciences Building, Oregon Health & Science University, Portland, OR, 97201, USA.
5Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, OR, 97239, USA.
CORRESPONDING AUTHOR : Gaurav Sahay
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause lethal pulmonary damage in humans. It contains spike proteins on its envelope that bind to human angiotensin-converting enzyme 2 (hACE2) expressed on airway cells, enabling entry of the virus, and causing infection. The soluble form of hACE2 binds SARS-CoV-2 spike protein, prevents viral entry into target cells, and ameliorates lung injury; however, its short half-life limits therapeutic utilities. Here, synthetic mRNA is engineered to encode a soluble form of hACE2 (hsACE2) to prevent viral infection. A novel lipid nanoparticle (LNP) is used for packaging and delivering mRNA to cells to produce hsACE2 proteins. Intravenously administered LNP delivers mRNA to hepatocytes, leading to the production of circulatory hsACE2 initiated within 2 h and sustained over several days. Inhaled LNP results in lung transfection and secretion of mucosal hsACE2 to lung epithelia, the primary site of entry and pathogenesis for SARS-CoV-2. Furthermore, mRNA-generated hsACE2 binds to the receptor-binding domain of the viral spike protein. Finally, hsACE2 effectively inhibits SARS-CoV-2 and its pseudoviruses from infecting host cells. The proof of principle study shows that mRNA-based nanotherapeutics can be potentially deployed to neutralize SARS-CoV-2 and open new treatment opportunities for coronavirus disease 2019 (COVID-19).
논문정보
- Research article
- 2022년 12월 (BRIC 등록일 2022-12-23)
- 국외 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
댓글 작성 로그인
팝업 닫기관련 링크
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기
