公开(公告)号：US11680275B2

公开(公告)日：2023-06-20

申请号：US16619733

申请日：2018-06-06

Applicant: UNIVERSITY OF MASSACHUSETTS

Inventor： Miguel Sena Esteves ,  Guangping Gao ,  Michael R. Green ,  Dan Wang ,  Tessa Mercedes Simone

IPC: C12N15/86 ,  C07K14/47

CPC classification number: C12N15/86 ,  C07K14/4702 ,  C07K2319/41 ,  C12N2310/141 ,  C12N2330/10 ,  C12N2750/14143

Abstract: In some aspects, the disclosure relates to compositions and methods of engineering a transgene. In some embodiments, the disclosure provides self-regulating recombinant nucleic acids, viral vectors and pharmaceutical compositions comprising a MeCP2 transgene. In some embodiments, compositions and methods described by the disclosure are useful for treating diseases and disorders associated with a loss of function mutation, for example Rett syndrome.

公开(公告)号：US20230151359A1

公开(公告)日：2023-05-18

申请号：US17910574

申请日：2021-03-08

Applicant: University of Massachusetts

Inventor： Dan Wang ,  Guangping Gao ,  Ailing Du

IPC: C12N15/11 ,  C12N15/86 ,  A61P43/00

CPC classification number: C12N15/11 ,  C12N15/86 ,  A61P43/00 ,  C12N2750/14143 ,  C12N2800/30

Abstract: In some aspects the disclosure provides compositions and methods for promoting expression of functional Forkhead box G1 (FOXG1) protein in a subject. In some embodiments, the disclosure provides methods of treating a subject having FOXG1 deficiency.

公开(公告)号：US20230121437A1

公开(公告)日：2023-04-20

申请号：US17768305

申请日：2020-10-14

Applicant: University of Massachusetts

Inventor： Guangping Gao ,  Dan Wang ,  Jiaming Wang

IPC: C12N15/11 ,  C12N9/22 ,  C12N15/86 ,  C12N9/78 ,  A61K48/00 ,  A61K38/46 ,  A61K31/7105

Abstract: Aspects of the disclosure relate to compositions and methods for exon replacement in a cell or a subject. In some embodiments, the disclosure relates to isolated nucleic acids (and vectors, such as rAAV vectors) encoding one or more guideRNAs (gRNAs) that target an intron-exon boundary; an intronic sequence having a splice signal; and a donor sequence encoding a gene product of a gene of interest, or portion thereof. In some embodiments, compositions described herein are useful for replacing mutant exons associated with certain diseases, for example Duchen's muscular dystrophy (DMD), cystic fibrosis (CF), spinal muscular atrophy (SMA), Rett syndrome, and mucopolysaccharidosis (MPS).

公开(公告)号：US20230089490A1

公开(公告)日：2023-03-23

申请号：US17767727

申请日：2020-10-09

Applicant: University of Massachusetts

Inventor： Guangping Gao ,  Craig Mendonca ,  Dan Wang

IPC: C12N15/113 ,  C12N15/86 ,  A61K48/00 ,  A61P7/00 ,  A61P11/00 ,  A61P21/00

Abstract: Aspects of the disclosure relate to compositions and methods for treating certain diseases associated with the presence of one or more premature stop codons in a gene, for example dominantly inherited diseases or recessively inherited diseases. In some embodiments, compositions comprise a vector (e.g., a viral vector, such as an rAAV vector) encoding one or more synthetic suppressor transfer RNAs (tRNAs) configured to read-through certain stop codons (e.g., premature stop codons). In some embodiments, the disclosure relates to methods for treating Hurler syndrome comprising administering such vectors to a subject.

公开(公告)号：US20230048017A1

公开(公告)日：2023-02-16

申请号：US17685457

申请日：2022-03-03

Applicant: University of Massachusetts

Inventor： Guangping Gao ,  Phillip Tai ,  Claudio Punzo ,  Haijiang Lin

IPC: C12N15/86 ,  C07K14/005 ,  C12N7/00 ,  A61K35/76 ,  A61P9/00

Abstract: Aspects of the disclosure relate to compositions and methods for expressing anti-Vascular endothelial cell growth factor (VEGF) agent in a cell or subject. In some embodiments, the disclosure provides rAAVs comprising a capsid protein (e.g., AAV2 variants, AAV2/3 hybrid variants, AAV8 variants, etc.), and a transgene encoding an anti-VEGF agent (e.g., KH902) and one or more regulatory sequences. In some embodiments, compositions described herein are useful for treating subjects having diseases associated with angiogenesis or aberrant VEGF activity/signaling.

公开(公告)号：US11578340B2

公开(公告)日：2023-02-14

申请号：US16341504

申请日：2017-10-13

Applicant: University of Massachusetts ,  Sichuan University

Inventor： Guangping Gao ,  Guangchao Xu ,  Phillip Tai ,  Yuquan Wei ,  Li Luo

IPC: C12N15/86 ,  A01K67/027 ,  A61K35/761 ,  C07K14/005 ,  C12N15/861 ,  C07K14/015 ,  A61K48/00

Abstract: The disclosure in some aspects relates to recombinant adeno-associated viruses having distinct tissue targeting capabilities. In some aspects, the disclosure relates to gene transfer methods using the recombinant adeno-associated viruses. In some aspects, the disclosure relates to isolated AAV capsid proteins and isolated nucleic acids encoding the same.

公开(公告)号：US20220233720A1

公开(公告)日：2022-07-28

申请号：US17612653

申请日：2020-05-19

Applicant: University of Massachusetts

Inventor： Guangping Gao ,  Hemant Khanna

IPC: A61K48/00 ,  C12N5/079 ,  C12N7/00 ,  C12N15/86 ,  C12N15/113 ,  C07K14/705 ,  A61K35/76 ,  A61P27/02

Abstract: Aspects of the disclosure relate to compositions and methods useful for treating ocular ciliopathies, for example Leber congenital amaurosis (LCA). In some embodiments, the disclosure provides isolated nucleic acids comprising a transgene encoding a CEP290 protein fragment, and methods of treating ocular ciliopathies using the same.

公开(公告)号：US20220177915A1

公开(公告)日：2022-06-09

申请号：US17541141

申请日：2021-12-02

Applicant: University of Massachusetts

Inventor： Jae-Hyuck Shim ,  Guangping Gao ,  Jun Xie ,  Yeon-Suk Yang ,  Jung Min Kim ,  Sachin Chaugule

IPC: C12N15/86 ,  C12N9/22 ,  A61P19/08 ,  C12N15/11

Abstract: In some aspects, the disclosure relates to compositions and methods for treating fibrodysplasia ossificans progressiva (FOP) in a subject. In some aspects, the disclosure provides isolated nucleic acids, and vectors such as rAAV vectors, configured to express transgenes that inhibit (e.g., decrease) expression of mutated AVCR1 gene in muscle cells or connective tissues.

公开(公告)号：US20220162641A1

公开(公告)日：2022-05-26

申请号：US17602343

申请日：2020-04-09

Applicant: University of Massachusetts

Inventor： Guangping Gao ,  Jun Xie

IPC: C12N15/86 ,  C07K14/47

Abstract: Aspects of the disclosure relate to compositions and methods for expressing a Factor H protein (or a variant thereof) in a cell or subject. In some embodiments, the disclosure provides isolated nucleic acids and rAAVs comprising a transgene encoding a Factor H protein variant and one or more regulatory sequences. In some embodiments, compositions described herein are useful for treating subjects having diseases associated with Factor H deficiency.

公开(公告)号：US20210380981A1

公开(公告)日：2021-12-09

申请号：US17342587

申请日：2021-06-09

Applicant: University of Massachusetts

Inventor： Guangping Gao ,  Yi Lu ,  Qiang Zheng ,  Xun Xu ,  Phillip D. Zamore ,  Phillip Tai

IPC: C12N15/113 ,  C12N15/86 ,  C12N15/11 ,  A61P27/02 ,  A61K9/00

Abstract: The disclosure relates, in some aspects, to compositions and methods for treating corneal disease (e.g., corneal neovascularization. In some embodiments, the disclosure relates to rAAV-mediated delivery of an cornea-associated transgene to a subject. In some embodiments, the rAAV transduces the corneal tissue of a subject.