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    COMPOSITIONS AND METHODS FOR ORGAN-PROTECTIVE EXPRESSION AND MODULATION OF CODING RIBONUCLEIC ACIDS
    6.
    发明公开
    COMPOSITIONS AND METHODS FOR ORGAN-PROTECTIVE EXPRESSION AND MODULATION OF CODING RIBONUCLEIC ACIDS 审中-公开

    公开(公告)号：EP4008333A1

    公开(公告)日：2022-06-08

    申请号：EP21205379.7

    申请日：2019-02-19

    申请人： Combined Therapeutics, Inc.

    发明人： MICOL, Romain

    IPC分类号： A61K31/7088 ,  C12N15/11 ,  A61K48/00

    摘要： Provided is an isolated mRNA sequence for expression of one or more cytokines within one or more target organs, the sequence comprising at least one coding sequence which codes for one or more cytokines (or their ligands) involved in immune response and inflammation selected from one or more of: TNFα, TNFβ, IFNα, IFNβ, IFNgamma, IL1, IL2, IL3, IL4, IL5, IL6, IL7, IL8, IL9, IL10, IL11, IL12, CCL2, CCL3, CCL4, CCL5, CXCL 9, and CXCL10. The sequence also comprises at least a first untranslated region (UTR) sequence, and at least three different micro-RNA (miRNA) binding site sequences. Each of the miRNA binding site sequences is located within, immediately 5' to or immediately 3' to, the first UTR sequence; and the miRNA binding site sequences allow for differential expression of the coding sequence in at least a first and a second cell type within the target organ or organs. Also provided are pharmaceutical compositions comprising the mRNA sequence, and methods for using the sequence or composition, particularly in treatment of disease, such as cancer of the liver, brain, lung, breast, pancreas, colon and kidney.