公开(公告)号：US20230265214A1

公开(公告)日：2023-08-24

申请号：US18043534

申请日：2021-08-31

申请人： YALE UNIVERSITY ,  GENNAO BIO, INC.

发明人： Elias Quijano ,  Peter Glazer ,  Bruce C. Turner ,  Audrey Turchick ,  W. Mark Saltzman

IPC分类号： C07K16/40 ,  C12N15/117 ,  A61P35/00

CPC分类号： C07K16/40 ,  C12N15/117 ,  A61P35/00 ,  C07K2317/565 ,  C07K2317/622 ,  C07K2317/24

摘要： Compositions and methods of use thereof for delivering nucleic acid cargo into cells are provided. The compositions typically include (a) a 3E10 monoclonal antibody or an antigen binding, cell-penetrating fragment thereof; a monovalent, divalent, or multivalent single chain variable fragment (scFv); or a diabody; or humanized form or variant thereof, and (b) a nucleic acid cargo including, for example, a nucleic acid encoding a polypeptide, a functional nucleic acid, a nucleic acid encoding a functional nucleic acid, or a combination thereof. Elements (a) and (b) are typically non-covalently linked to form a complex.

公开(公告)号：US20210340280A1

公开(公告)日：2021-11-04

申请号：US17272136

申请日：2019-08-30

申请人： Yale University

发明人： Elias Quijano ,  Audrey Turchick ,  Peter Glazer

IPC分类号： C07K16/44 ,  A61K47/69 ,  A61K35/14 ,  A61K31/7088 ,  C12N15/10 ,  A61K48/00 ,  A61P43/00

摘要： Compositions for enhanced gene editing and methods of use thereof are. The composition contains a cell-penetrating antibody and a donor oligonucleotide containing a sequence that can correct a mutation in a cell's genome. Preferably, the composition does not contain a nuclease, PNA, or nanoparticle. The compositions are used to modify the genome of a cell by contacting the cell with an effective amount of the composition. Genomic modification occurs at a higher frequency both ex vivo and in vivo, when cells are contacted with the cell-penetrating antibody and donor oligonucleotide as compared to the absence of the cell-penetrating antibody.

公开(公告)号：US20210338815A1

公开(公告)日：2021-11-04

申请号：US17272151

申请日：2019-08-30

申请人： Yale University

发明人： Elias Quijano ,  Adele Ricciardi ,  Raman Bahal ,  Audrey Turchick ,  Nicholas Economos ,  W. Mark Saltzman ,  Peter Glazer

IPC分类号： A61K39/395 ,  A61K31/7088 ,  A61K38/46 ,  A61K9/51 ,  A61K35/28 ,  A61K38/14 ,  A61P7/00

摘要： Compositions for improved gene editing and methods of use thereof are disclosed. In a preferred method, gene editing involves use of a cell-penetrating anti-DNA antibody, such as 3E10, as a potentiating agent to enhance gene editing by nucleases and triplex forming oligonucleotides. Genomic modification occurs at a higher frequency when cells are contacted with the potentiating agent and nuclease or triplex forming oligonucleotide, as compared to the absence of the potentiating agent. The methods are suitable for both ex vivo and in vivo approaches to gene editing and are useful for treating a subject with a genetic disease or disorder. Nanoparticle compositions for intracellular delivery of the gene editing compositions are provided and are particularly advantageous for use with in vivo applications.

公开(公告)号：US20210340279A1

公开(公告)日：2021-11-04

申请号：US17272124

申请日：2019-08-30

申请人： Yale University

发明人： Peter Glazer ,  Audrey Turchick

IPC分类号： C07K16/44 ,  A61K45/06

摘要： Combination therapies including administering a subject in need thereof a cell-penetrating binding protein, such as an antibody, and an immune checkpoint modulator are provided. Typically, the cell-penetrating binding protein can induce DNA damage or reduce DNA damage repair in an effective amount to activate the innate immunity inflammatory pathway in target cells such as cancer cells or infected cells. For example, in some embodiments, the cell-penetrating binding protein increases induced p21 and/or p27 protein expression, increases accumulation of single-strand DNA in the cytosol, increases phosphorylation of STAT1, or a combination thereof in target cells. The subject can have cancer or an infection and the combination of the cell-penetrating binding protein and the immune checkpoint modulator reduce one or more symptoms of cancer or infection, preferably to a greater degree than administering the subject the same amount of cell-penetrating binding protein alone or the same amount of immune checkpoint modulator alone.