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Peptidic defective interfering gene nanoparticles against Omicron, Delta SARS-CoV-2 variants and influenza A virus in vivo.
Zhao, Hanjun; Zhang, Chuyuan; Lam, Hoiyan; Meng, Xinjie; Peng, Zheng; Yeung, Man Lung; Chan, Jasper Fuk-Woo; Kai-Wang To, Kelvin; Yuen, Kwok-Yung.
  • Zhao H; State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China. hjzhao13@hku.hk.
  • Zhang C; Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China. hjzhao13@hku.hk.
  • Lam H; Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, China. hjzhao13@hku.hk.
  • Meng X; Department of Infectious Disease and Microbiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong Province, China. hjzhao13@hku.hk.
  • Peng Z; Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
  • Yeung ML; Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
  • Chan JF; Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
  • Kai-Wang To K; Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, China.
  • Yuen KY; Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
Signal Transduct Target Ther ; 7(1): 266, 2022 08 03.
Article Dans Anglais | MEDLINE | ID: covidwho-1972575
ABSTRACT
Defective interfering genes (DIGs) are short viral genomes and interfere with wild-type viral replication. Here, we demonstrate that the new designed SARS-CoV-2 DIG (CD3600) can significantly inhibit the replication of SARS-CoV-2 including Alpha, Delta, Kappa and Omicron variants in human HK-2 cells and influenza DIG (PAD4) can significantly inhibit influenza virus replication in human A549 cells. One dose of influenza DIGs prophylactically protects 90% mice from lethal challenge of A(H1N1)pdm09 virus and CD3600 inhibits SARS-CoV-2 replication in hamster lungs when DIGs are administrated to lungs one day before viral challenge. To further investigate the gene delivery vector in the respiratory tract, a peptidic TAT2-P1&LAH4, which can package genes to form small spherical nanoparticles with high endosomal escape ability, is demonstrated to dramatically increase gene expression in the lung airway. TAT2-P1&LAH4, with the dual-functional TAT2-P1 (gene-delivery and antiviral), can deliver CD3600 to significantly inhibit the replication of Delta and Omicron SARS-CoV-2 in hamster lungs. This peptide-based nanoparticle system can effectively transfect genes in lungs and deliver DIGs to inhibit SARS-CoV-2 variants and influenza virus in vivo, which provides the new insight into the drug delivery system for gene therapy against respiratory viruses.
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Texte intégral: Disponible Collection: Bases de données internationales Base de données: MEDLINE Sujet Principal: Virus de la grippe A / Grippe humaine / Sous-type H1N1 du virus de la grippe A / Nanoparticules / COVID-19 Les sujets: Vaccins / Variantes Limites du sujet: Animaux / Humains langue: Anglais Revue: Signal Transduct Target Ther Année: 2022 Type de document: Article Pays d'affiliation: S41392-022-01138-0

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Texte intégral: Disponible Collection: Bases de données internationales Base de données: MEDLINE Sujet Principal: Virus de la grippe A / Grippe humaine / Sous-type H1N1 du virus de la grippe A / Nanoparticules / COVID-19 Les sujets: Vaccins / Variantes Limites du sujet: Animaux / Humains langue: Anglais Revue: Signal Transduct Target Ther Année: 2022 Type de document: Article Pays d'affiliation: S41392-022-01138-0