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    MTOR -TARGETED MODIFICATION AND USES THEREOF
    1.
    发明公开
    MTOR -TARGETED MODIFICATION AND USES THEREOF 审中-公开

    公开(公告)号：US20240352487A1

    公开(公告)日：2024-10-24

    申请号：US18682277

    申请日：2022-08-05

    Applicant: UNIVERSITÉ LAVAL

    Inventor： Sébastien LEVESQUE ,  Yannick DOYON

    IPC: C12N15/90 ,  C12N9/12 ,  C12N9/22 ,  C12N15/11

    CPC classification number: C12N15/907 ,  C12N9/1276 ,  C12N9/22 ,  C12N15/11 ,  C12Y207/07049 ,  C07K2319/00 ,  C12N2310/20

    Abstract: Described herein are reagents, products, methods, and uses thereof for modifying the genome of a cell at a MTOR locus, for example by nuclease-based (e.g. CRISPR/Cas9) modification. The modifications include a MTOR modification which confers resistance to an mTOR inhibitor. The modifications may further include a modification to introduce a nucleic acid or gene of interest. Introducing both modifications at the MTOR locus is an efficient and advantageous strategy which allows for targeted modification of both aspects (resistance and gene of interest) at the same locus, and further allows for the use of an mTOR inhibitor to select and enrich for such modified cells. Such modified cells may be used for a variety of applications, including therapeutic applications.

    METHODS AND COMPOSITIONS FOR PRIME EDITING NUCLEOTIDE SEQUENCES
    7.
    发明公开
    METHODS AND COMPOSITIONS FOR PRIME EDITING NUCLEOTIDE SEQUENCES 审中-公开

    公开(公告)号：US20240229077A1

    公开(公告)日：2024-07-11

    申请号：US18064738

    申请日：2022-12-12

    Applicant: The Broad Institute, Inc. ,  President and Fellows of Harvard College

    Inventor： David R. Liu ,  Andrew Vito Anzalone ,  James William Nelson

    IPC: C12N15/90 ,  C12N9/12 ,  C12N9/22 ,  C12N15/11

    CPC classification number: C12N15/907 ,  C12N9/1276 ,  C12N9/22 ,  C12N15/11 ,  C12N15/111 ,  C12N2310/20 ,  C12N2800/80

    Abstract: The present disclosure provides compositions and methods for conducting prime editing of a target DNA molecule (e.g., a genome) that enables the incorporation of a nucleotide change and/or targeted mutagenesis. The nucleotide change can include a single-nucleotide change (e.g., any transition or any transversion), an insertion of one or more nucleotides, or a deletion of one or more nucleotides. More in particular, the disclosure provides fusion proteins comprising nucleic acid programmable DNA binding proteins (napDNAbp) and a polymerase (e.g., reverse transcriptase), which is guided to a specific DNA sequence by a modified guide RNA, named an PEgRNA. The PEgRNA has been altered (relative to a standard guide RNA) to comprise an extended portion that provides a DNA synthesis template sequence which encodes a single strand DNA flap, which is homologous to a strand of the targeted endogenous DNA sequence to be edited, but which contains the desired one or more nucleotide changes and which, following synthesis by the polymerase (e.g., reverse transcriptase), becomes incorporated into the target DNA molecule. Also disclosed herein are various methods that leverage prime editing, including treating trinucleotide repeat contraction diseases, installing targeted peptide tags, treating prion disease through the installation of protection mutations, manipulating RNA-encoding genes for the installation of RNA tags for controlling the function and expression of RNA, using prime editing to construct sophisticated gene libraries, using prime editing to insert immunoepitopes into proteins, use of prime editing to insert inducible dimerization domains into protein targets, and delivery methods, among others.

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