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18 条记录 (耗时 0.01 秒)

    BILE SALTS BACTOSENSOR AND USE THEREOF FOR DIAGNOSTIC AND THERAPEUTIC PURPOSES
    6.
    发明申请
    BILE SALTS BACTOSENSOR AND USE THEREOF FOR DIAGNOSTIC AND THERAPEUTIC PURPOSES 审中-公开

    公开(公告)号：WO2021255084A1

    公开(公告)日：2021-12-23

    申请号：PCT/EP2021/066224

    申请日：2021-06-16

    申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) ,  UNIVERSITÉ DE MONTPELLIER

    发明人： BONNET, Jérôme ,  CHANG, Hung Ju ,  GRACY, Jérôme ,  COHEN-GONSAUD, Martin

    IPC分类号： C12N15/63 ,  C12Q1/6897 ,  C07K14/28 ,  C07K2319/71 ,  C12N15/635 ,  C12N15/70

    摘要： Bile salts are steroid acids derived from cholesterol in the liver, are released into the gastrointestinal tract to aid in digestion and are thoroughly modified by the resident gut microbiota. Bile acids act as versatile signaling molecules with a variety of endocrine functions and are linked to several diseases. In particular, serum and urinary bile salts represent biomarkers for early diagnostics of liver dysfunction, yet their current detection methods are impractical and hard to scale. Here the inventors engineered engineered synthetic bile salt receptors using TcpP as sensing domains connected to E. coli CadC system which activates transcription upon dimerization. The performance of the system was assayed for various selection of promoters and they can show that fine tunable response that may be reached by changing expression levels of the bile salt receptor. By performing multiple rounds of directed evolution of the TcpP sensor the inventors obtained a collection of variants with a lower limit of detection and a higher sensitivity. Finally, they show that their bactosensor can detect pathological bile-salt concentrations in samples from patients with liver dysfunction. The present invention thus relates to bile salts bactosensor and use thereof for diagnostic and therapeutic purposes.

    INDUCIBLE CONTROL OF GENE EXPRESSION
    8.
    发明申请
    INDUCIBLE CONTROL OF GENE EXPRESSION 审中-公开

    公开(公告)号：WO2022020431A2

    公开(公告)日：2022-01-27

    申请号：PCT/US2021/042515

    申请日：2021-07-21

    申请人： TRUSTEES OF BOSTON UNIVERSITY

    发明人： WONG, Wilson ,  DING, Yage

    IPC分类号： C07K19/00 ,  C12N15/79 ,  C12N9/22 ,  C12N9/90 ,  C12N15/63 ,  C07K2319/00 ,  C12N15/635 ,  C12N9/1241

    摘要： The technology described herein is directed to inducible and repressible polypeptides and polypeptide systems. In particular, described herein are split sequence-specific nucleases and split recombinases that are linked to drug-inducible or drug-repressible dimerization domains. In some embodiments, the polypeptides comprise sequestering domains and/or have their expression controlled by an inducible promoter. In multiple aspects described herein are polynucleotides, vectors, cells, and pharmaceutical compositions comprising said polypeptides or polypeptide systems. Also described herein are methods of using said polypeptide systems to modulate the expression of a target polypeptide or to treat a subject in need of a cell therapy.

    NUCLEOTIDES COMPRISING CASPHI MODIFIED FOR NUCLEAR TARGETING
    10.
    发明申请
    NUCLEOTIDES COMPRISING CASPHI MODIFIED FOR NUCLEAR TARGETING 审中-公开

    公开(公告)号：WO2023028254A2

    公开(公告)日：2023-03-02

    申请号：PCT/US2022/041561

    申请日：2022-08-25

    申请人： VANDERBILT UNIVERSITY

    发明人： REX, Tonia S. ,  BACKSTROM, Jon R.

    IPC分类号： C12N15/09 ,  C12N15/11 ,  C12N15/63 ,  C12N15/79 ,  C12N15/85 ,  C12N15/86 ,  C12N15/87 ,  C12N15/90 ,  A61K48/00 ,  C12N15/00 ,  C12N15/102 ,  C12N15/635 ,  C12N2310/20 ,  C12N2750/14143

    摘要： The presently-disclosed subject matter relates to a compositions and methods that makes use of a CasΦ(CasPhi) that has been modified for effective nuclear targeting. In particular, certain embodiments of the presently-disclosed subject matter relate to unique nucleic acid molecules, compositions, and methods for delivery of CasPhi to the nucleus to effectively modulate expression or otherwise target of a gene of interest. A nucleic acid disclosed herein includes a nucleotide encoding a CasPhi, wherein there are no amino acid substitutions, or wherein proline residues at amino acids 749 and 753 have been substituted; a nucleotide encoding an amino-terminal linker connected to the amino-terminal end of the CasPhi; a nucleotide encoding a carboxy -terminal linker connected to the carboxy-terminal end of the CasPhi; and a nucleotide encoding a nuclear localization signal (NLS) downstream from the CasPhi and carboxy-terminal linker.