公开(公告)号：US20240335560A1

公开(公告)日：2024-10-10

申请号：US18466517

申请日：2023-09-13

申请人： 4D MOLECULAR THERAPEUTICS INC.

发明人： David H. Kirn ,  Melissa KOTTERMAN ,  David SCHAFFER ,  Paul SZYMANSKI ,  Peter FRANCIS

IPC分类号： A61K48/00 ,  A61K9/00 ,  C07K14/005 ,  C07K16/22 ,  C12N7/00

CPC分类号： A61K48/005 ,  A61K9/0048 ,  A61K48/0008 ,  A61K48/0075 ,  C07K14/005 ,  C07K16/22 ,  C12N7/00 ,  C12N2750/14122 ,  C12N2750/14143

摘要： Provided herein are variant adeno-associated virus (AAV) capsid proteins having one or more modifications in amino acid sequence relative to a parental AAV capsid protein, which, when present in an AAV virion, confer increased infectivity of one or more types of retinal cells as compared to the infectivity of the retinal cells by an AAV virion comprising the unmodified parental AAV capsid protein. Also provided are recombinant AAV virions and pharmaceutical compositions thereof comprising a variant AAV capsid protein as described herein, methods of making these rAAV capsid proteins and virions, and methods for using these rAAV capsid proteins and virions in research and in clinical practice, for example in, e.g., the delivery of nucleic acid sequences to one or more cells of the retina, for the treatment of retinal disorders and diseases.

公开(公告)号：US12102691B2

公开(公告)日：2024-10-01

申请号：US17350769

申请日：2021-06-17

申请人： Massachusetts Eye and Ear Infirmary ,  President and Fellows of Harvard College

发明人： Zheng-Yi Chen ,  David R. Liu ,  Margie Li ,  David B. Thompson ,  John Zuris

IPC分类号： A61K48/00 ,  A61K9/127 ,  A61K38/00 ,  A61K38/10 ,  A61K47/64 ,  A61K47/69 ,  C07J7/00 ,  C07K7/06 ,  C07K7/08 ,  C07K14/46 ,  C07K14/47 ,  C07K19/00 ,  C12N5/0793 ,  C12N9/00 ,  C12N9/22 ,  C12N9/52 ,  C12N15/11 ,  C12N15/113 ,  C12N15/87 ,  C12N15/88 ,  C12N15/90

CPC分类号： A61K48/0008 ,  A61K9/1272 ,  A61K38/00 ,  A61K38/10 ,  A61K47/64 ,  A61K47/6911 ,  A61K48/0075 ,  A61K48/0083 ,  C07J7/009 ,  C07K7/06 ,  C07K7/08 ,  C07K14/463 ,  C07K14/47 ,  C07K19/00 ,  C12N5/062 ,  C12N9/00 ,  C12N9/22 ,  C12N9/52 ,  C12N15/11 ,  C12N15/113 ,  C12N15/87 ,  C12N15/88 ,  C12N15/907 ,  C12Y304/2207 ,  C07K2319/06 ,  C07K2319/21 ,  C07K2319/33 ,  C07K2319/60 ,  C12N2310/20 ,  C12N2310/3513 ,  C12N2510/00

摘要： Compositions are described for direct protein delivery into multiple cell types in the mammalian inner ear. The compositions are used to deliver protein(s) (such as gene editing factors) editing of genetic mutations associated with deafness or associated disorders thereof. The delivery of genome editing proteins for gene editing and correction of genetic mutations protect or restore hearing from genetic deafness. Methods of treatment include the intracellular delivery of these molecules to a specific therapeutic target.

公开(公告)号：US12031146B2

公开(公告)日：2024-07-09

申请号：US17322561

申请日：2021-05-17

申请人： The Board of Trustees of the Leland Stanford Junior University

发明人： Adi Barzel ,  Mark A. Kay

IPC分类号： A61K39/00 ,  A61K38/18 ,  A61K39/395 ,  A61K48/00 ,  C07K14/705 ,  C07K14/71 ,  C07K14/715 ,  C07K16/10 ,  C07K16/28 ,  C12N5/0783 ,  C12N9/64 ,  C12N15/00 ,  C12N15/52 ,  C12N15/86 ,  C12N15/90

CPC分类号： C12N15/86 ,  A61K38/1866 ,  A61K48/0008 ,  A61K48/005 ,  C07K16/1045 ,  C12N9/644 ,  C12N15/52 ,  C12N15/907 ,  C12Y304/21022 ,  C07K2317/76 ,  C07K2319/92 ,  C12N2750/14143 ,  C12N2799/025 ,  C12N2800/24 ,  C12N2840/20 ,  Y02A50/30

摘要： Methods and compositions are provided for editing the genome of a cell without the use of an exogenously supplied nuclease. Aspects of the methods include contacting a cell with a targeting vector comprising nucleic acid sequence to be integrated into the target locus, where the cell is not also contacted with a nuclease. In addition, reagents, devices and kits thereof that find use in practicing the subject methods are provided.

公开(公告)号：US20240218391A1

公开(公告)日：2024-07-04

申请号：US18289031

申请日：2022-05-04

申请人： Decibel Therapeutics, Inc.

发明人： Joseph BURNS ,  Tyler GIBSON ,  Gabriela PREGERNIG ,  Kathy SO

IPC分类号： C12N15/86 ,  A61K48/00 ,  C07K14/47

CPC分类号： C12N15/86 ,  A61K48/0008 ,  C07K14/4705 ,  C12N2750/14143 ,  C12N2830/008

摘要： The disclosure provides polynucleotides containing SLC6A14 promoters, as well as vectors containing the same, that can be used to promote expression of a transgene in vestibular supporting cells. The polynucleotides described herein may be operably linked to a transgene, such as a transgene encoding a protein of interest, so as to promote vestibular supporting cell expression of the transgene. The polynucleotides described herein may be operably linked to a transgene and used for the treatment of subjects having or at risk of developing vestibular dysfunction.

公开(公告)号：US20240150734A1

公开(公告)日：2024-05-09

申请号：US18051109

申请日：2022-10-31

申请人： Poseida Therapeutics, Inc.

发明人： Eric M. OSTERTAG ,  Blair MADISON

IPC分类号： C12N9/12 ,  A01K67/0275 ,  A61D19/04 ,  A61K48/00 ,  C12N9/22 ,  C12N15/85

CPC分类号： C12N9/1241 ,  A01K67/0275 ,  A61D19/04 ,  A61K48/0008 ,  C12N9/22 ,  C12N15/8509 ,  C12Y207/07 ,  A01K67/0333

摘要： The present invention provides PiggyBac transposase proteins, nucleic acids encoding the same, compositions comprising the same, kits comprising the same, non-human transgenic animals comprising the same, and methods of using the same.

公开(公告)号：US20240124894A1

公开(公告)日：2024-04-18

申请号：US18487398

申请日：2023-10-16

申请人： KING'S COLLEGE LONDON ,  ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

发明人： Ralph Michael LINDEN

IPC分类号： C12N15/86 ,  A61K48/00 ,  A61P1/16 ,  A61P25/00 ,  A61P27/02 ,  A61P27/06 ,  C07K14/005

CPC分类号： C12N15/86 ,  A61K48/0008 ,  A61P1/16 ,  A61P25/00 ,  A61P27/02 ,  A61P27/06 ,  C07K14/005 ,  C12N2750/14122 ,  C12N2750/14142 ,  C12N2750/14143

摘要： Disclosed herein is a recombinant adeno-associated virus (AAV) vector comprising (a) a variant AAV2 capsid protein, wherein the variant AAV2 capsid protein comprises at least four amino acid substitutions with respect to a wild type AAV2 capsid protein; wherein the at least four amino acid substitutions are present at the following positions in an AAV2 capsid protein sequence: 457, 492, 499 and 533; and (b) a heterologous nucleic acid comprising a nucleotide sequence encoding a gene product.

公开(公告)号：US20240075110A1

公开(公告)日：2024-03-07

申请号：US18467826

申请日：2023-09-15

申请人： CUROGEN TECHNOLOGY CO., LTD. ,  RESEARCH & BUSINESS FOUNDATION SUNGKYUNKWAN UNIVERSITY

发明人： Chang Woo LEE ,  Jin Kwan LEE ,  Hyun Soo KIM ,  Ji Hyun CHOI ,  Se Eun BYEON ,  HAE IN LEE ,  HYEONJU JO

IPC分类号： A61K38/46 ,  A61K48/00 ,  A61P1/16

CPC分类号： A61K38/465 ,  A61K48/0008 ,  A61K48/0058 ,  A61P1/16

摘要： The present invention provides a method for preventing or treating a liver disease selected from the group consisting of non-alcoholic fatty liver, non-alcoholic steatohepatitis and hepatic fibrosis comprising administrating at least one selected from the group consisting of an Ssu72 peptide, a polynucleotide encoding the Ssu72 peptide, and an expression vector comprising the polynucleotide.

公开(公告)号：US20230416777A1

公开(公告)日：2023-12-28

申请号：US18038976

申请日：2021-06-15

申请人： YUNZHOU BIOSCIENCES (GUANGZHOU) CO., INC.

发明人： Jinxiu SHI ,  Weineng MENG ,  Yan LUO ,  Yingjun LIN ,  Shengzhi LIN

IPC分类号： C12N15/86 ,  C12N15/65 ,  A61K48/00

CPC分类号： C12N15/86 ,  C12N15/65 ,  A61K48/0008 ,  C12N2800/107 ,  C12N2820/55 ,  C12N2830/48 ,  C12N2830/50 ,  C12N2740/13043 ,  C12N2740/13052

摘要： Provided are a Moloney murine leukemia virus-based self-inactivating vector and applications thereof. The self-inactivating vector comprises: 5′LTR, a target expression gene or multiple cloning sites used for inserting the target expression gene, 3′LTR, and a polyadenylated nucleic acid fragment, where the nucleic acid fragment between the Pvu II enzyme cutting site and the Sac I enzyme cutting site of the U3 region of 5′LTR is replaced by a CMV enhancer and a CMV promoter connected to the CMV enhancer, the nucleic acid fragment between the Pvu II enzyme cutting site and the Sac I enzyme cutting site of the U3 region of 3′LTR is deleted, and the polyadenylated nucleic acid fragment is located at the 3′-terminus of 3′LTR. The self-inactivating vector, serving as a vector for a gene therapy, provides increased safeness and a high virus titer, and allows the high-efficiency expression of a target gene.

公开(公告)号：US20230405149A1

公开(公告)日：2023-12-21

申请号：US18038247

申请日：2021-11-24

申请人： Prevail Therapeutics, Inc.

发明人： Asa Abeliovich ,  Sitharthan Kamalakaran ,  Benjamin Shykind ,  Edmund c. Schwartz ,  Anindya Kumar Sen

IPC分类号： A61K48/00 ,  A61P25/28

CPC分类号： A61K48/005 ,  A61P25/28 ,  A61K48/0008 ,  A61K48/0075

摘要： The disclosure relates, in some aspects, to compositions and methods for treatment of neurodegenerative disease, for example Alzheimer's disease. In some embodiments, the disclosure provides expression constructs comprising a transgene encoding an APOE Christchurch (e.g., APOE3ch and/or APOE2ch) protein isoform or a portion thereof, an inhibitory nucleic acid targeting an APOE gene or a portion thereof, or any combination of the foregoing. In some embodiments, the disclosure provides methods of treating Alzheimer's disease by administering an expression construct to a subject in need thereof.

公开(公告)号：US20230323311A1

公开(公告)日：2023-10-12

申请号：US18184184

申请日：2023-03-15

申请人： The Regents of the University of California

发明人： David V. Schaffer ,  Melissa A. Kotterman ,  Bum-Yeol Hwang ,  James T. Koerber

IPC分类号： C12N7/00 ,  C07K14/005 ,  A61K35/761 ,  C12N15/86 ,  A61K48/00 ,  C07K14/00 ,  C12N5/071 ,  C12N15/113 ,  A61K35/76 ,  C12N15/10

CPC分类号： C12N7/00 ,  C07K14/005 ,  A61K35/761 ,  C12N15/86 ,  A61K48/0008 ,  C07K14/001 ,  C12N5/0686 ,  C12N15/113 ,  A61K35/76 ,  A61K48/005 ,  C12N15/1058 ,  C12N2750/14122 ,  C12N2750/14143 ,  C12N2310/14 ,  C12N2750/14142

摘要： The present disclosure provides infectious recombinant adeno-associated virus (rAAV) virions that comprise a variant capsid protein and a heterologous nucleic acid. The present disclosure further provides the variant adeno-associated virus (AAV) capsid proteins (and/or a nucleic acid encoding the variant AAV capsid proteins), which confer to an infectious rAAV virion an increased resistance to human AAV neutralizing antibodies. The present disclosure further provides host cells comprising an infectious rAAV virion and/or a nucleic acid encoding a subject variant AAV capsid protein. The present disclosure further provides methods of delivering a heterologous nucleic acid to a target cell where the target cell is contacted with a subject infectious rAAV virion. The present disclosure further provides methods of delivering a gene product to an individual, the methods generally involving administering an effective amount of a subject rAAV virion to an individual in need thereof.