Peptidic defective interfering gene nanoparticles against Omicron,Delta SARS-CoV-2 variants and influenza A virus in vivo

作     者：Hanjun Zhao Chuyuan Zhang Hoiyan Lam Xinjie Meng Zheng Peng Man Lung Yeung Jasper Fuk-Woo Chan Kelvin Kai-Wang To Kwok-Yung Yuen 

作者机构：State Key Laboratory of Emerging Infectious DiseasesLi Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina Department of MicrobiologySchool of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina Centre for VirologyVaccinology and TherapeuticsHong Kong Science and Technology ParkHong Kong Special Administrative RegionChina Department of Infectious Disease and MicrobiologyThe University of Hong Kong-Shenzhen HospitalShenzhenGuangdong ProvinceChina Carol Yu Centre for InfectionThe University of Hong KongPokfulamHong Kong Special Administrative RegionChina Guangzhou LaboratoryGuangzhouGuangdong ProvinceChina 

出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)

年 卷 期：2022年第7卷第9期

页      面：3484-3493页

核心收录：

学科分类：0710[理学-生物学] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 100401[医学-流行病与卫生统计学] 10[医学] 

基　　金：This study was supported by fundings from Health@InnoHK,Innovation and Technology Commission,the Government of the Hong Kong Special Administrative Region the Health and Medical Research Fund,the Government of the Hong Kong Special Administrative Region(COVID1903010 Project 13) the National Program on Key Research Project of China(2020YFA0707500) Theme-Based Research Scheme of the Research Grants Council(11-709/21-N),Emergency Key Program of Guangzhou Laboratory(EKPG22-01) the National Key Research and Development Programme on Public Security Risk Prevention and Control Emergency Project,the Health and Medical Research Fund(22210792) donations of Michael Seak-Kan Tong,Richard Yu and Carol Yu,Lee Wan Keung Charity Foundation Limited,May Tam Mak Mei Yin,Respiratory Viral Research Foundation Limited,the Shaw Foundation Hong Kong,Hui Ming,Hui Hoy and Chow Sin Lan Charity Fund Limited,Chan Yin Chuen Memorial Charitable Foundation,The Chen Wai Wai Vivien Foundation Limited,and Marina Man-Wai Lee.We thanks Dr Jenny K.W.Lam for providing LAH4 for the experiments 

主　　题：influenza vivo Delta 

摘      要：Defective interfering genes(DIGs)are short viral genomes and interfere with wild-type viral ***,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 *** 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 *** 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 ***2-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 *** 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.