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    Home > Biochemistry News > Biotechnology News > Wei Wensheng's research group from the School of Life Sciences reports on the circular RNA technology platform and the new anti-new coronavirus vaccine developed accordingly

    Wei Wensheng's research group from the School of Life Sciences reports on the circular RNA technology platform and the new anti-new coronavirus vaccine developed accordingly

    • Last Update: 2022-05-20
    • Source: Internet
    • Author: User
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    On March 31, 2022, Wei Wensheng's group from Peking University School of Life Sciences published a research paper titled " Circular RNA Vaccines against SARS-CoV-2 and Emerging Variants " online in the journal Cell , reporting for the first time a circular RNA vaccine technology platform , and the circular RNA vaccine developed against the new coronavirus and its series of variants .
    The circular RNA vaccine (circRNA RBD-Delta ) against the new coronavirus delta variant prepared in this study has broad-spectrum protection against a variety of new coronavirus variants (Figure 1) .

    Figure 1 Schematic diagram of the development of 2019-nCoV circRNA vaccine

    As a breakthrough medical technology emerging in recent years, the basic principle of mRNA vaccine is to express antigen protein by introducing mRNA into the body through lipid nanoparticles (LNP) to stimulate the body to produce a specific immune response
    After the outbreak of the novel coronavirus pneumonia (COVID-19) in late 2019, a targeted mRNA vaccine (ModernamRNA-1273; Pfizer/BioNTechBNT162b2) stood out among various vaccine types

    The modification and delivery technologies of mRNA vaccines are produced by foreign institutions, which restrict the development and application of mRNA vaccines and their therapeutic technologies in China.
    Therefore, there is an urgent need to develop new and efficient vaccine technologies

    Different from linear mRNA, circular RNA molecules have a covalently closed ring structure without 5'-Cap and 3'-polyA structure; and do not need to introduce modified bases, and their stability is higher than linear RNA

    However, the circularization method and purification strategy of RNA are still immature, and the impact of its potential immunogenicity on vaccine development is not clear.
    Many unknown factors restrict the development and application of circular RNA


    Wei Wensheng's team first established a technical platform for the efficient preparation of high-purity circular RNA in vitro, and designed a circular RNA vaccine encoding the new coronavirus spike protein (Spike) receptor domain (RBD) for the new coronavirus and its variants
    Experiments have shown that the vaccine can induce high levels of 2019-nCoV neutralizing antibodies and specific T-cell immune responses in mice and rhesus monkeys, and can effectively reduce the viral load in the lungs of 2019-nCoV-infected rhesus monkeys.
    Significantly relieved the symptoms of pneumonia caused by new coronavirus infection (Figure 2)


    Figure 2 CircRNA vaccination provides significant protection in mice and rhesus monkeys

    A series of comparative evaluations showed that compared with mRNA vaccines, circRNA vaccines have the following characteristics or advantages (Figure 3): 1) circRNAs have higher stability and can generate higher levels and more durable antigens in vivo; 2) The proportion of neutralizing antibodies induced by circRNA vaccine is higher, which can more effectively fight against virus mutation and reduce the potential side effects of antibody-dependent enhancement (ADE) of vaccine; 3) The ratio of IgG2/IgG1 induced by circRNA vaccine is higher, indicating that It mainly induces a Th1-type protective T cell immune response, which can effectively reduce the potential side effects of vaccine-associated respiratory diseases (VAERD, Vaccine-associated enhanced respiratory diseases)

    Figure 3 Features and advantages of circRNA vaccines (compared to mRNA vaccines)

    In addition, after the new coronavirus Omicron mutant was listed as a Variants of Concern (VOC) by the World Health Organization, the research team urgently launched the development of a circular RNA vaccine for the mutant
    Within 30 days of obtaining the virus sequence information, the whole process from vaccine production, mouse immunization to efficacy evaluation was completed

    The study found that the circular RNA vaccine (circRNA
    RBD-Omicron ) based on the Omicron variant has a narrow range of protection, and the antibodies induced by it can only neutralize the Omicron variant
    The circular RNA vaccine (circRNA
    RBD-Delta ) designed for the delta variant can induce broad-spectrum neutralizing antibodies in mice, effectively neutralizing a variety of new crown variants including the Omicron strain.
    (Figure 4)


    Figure 4 The circRNA RBD-Delta vaccine designed for the new coronavirus delta variant is a candidate vaccine with broad-spectrum protection

    The above results show that the circRNA RBD-Delta vaccine designed for the new coronavirus delta variant is a candidate vaccine for new coronavirus pneumonia with broad-spectrum protection.
    This study also provides a vaccine development and vaccination strategy for the current rapid spread of the new coronavirus variant.
    Reference basis

    At the same time, the establishment of this platform-based technology has broad application prospects in the prevention or treatment of infectious diseases, autoimmune diseases, rare diseases and cancer


    Quan Liang, a postdoctoral fellow in Wei Wensheng's research group at Peking University, and Yi Zongyi and Shen Yong, a doctoral student, are the co-first authors of the paper
    This research has been supported and helped by many cooperative laboratories, including the research group of Professor Xie Xiaoliang/Researcher Cao Yunlong of Peking University, the research group of Professor Wang Jianwei of Chinese Academy of Medical Sciences/Peking Union Medical College, and Professor Peng Xiaozhong of Institute of Medical Biology, Chinese Academy of Medical Sciences The research group, the Wang Youchun research group and the Huang Weijin research group of the China National Institute for Food and Drug Control

    The research project has been supported by the National Key R&D Program, National Natural Science Foundation of China Key and General Program, Beijing Municipal Science and Technology Commission Biomedical Frontier Innovation Promotion Project, Beijing Future Genetic Diagnosis Advanced Innovation Center, Peking University-Tsinghua Life Science Joint Center and Infectious Diseases Supported by the National Science and Technology Major Project for Disease Prevention and Control

    Quanliang was supported by the 2020 National "Boxin Plan" Fund


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