公开(公告)号：US20250011812A1

公开(公告)日：2025-01-09

申请号：US18712273

申请日：2022-11-22

Applicant: University of Massachusetts

Inventor： Jun Xie ,  Guangping Gao ,  Qing Xie ,  Hong Ma

IPC: C12N15/86 ,  A61K48/00 ,  A61P25/00

Abstract: Aspects of the disclosure relate to compositions and methods for treating spinal muscular atrophy (SMA). The disclosure is based, in part, on isolated nucleic acids and vectors (e.g., viral vectors, such as rAAV vectors) encoding SMN1. In some embodiments, the expression of SMN 1 is driven by a native SMN 1 promoter or a variant thereof. In some embodiments, isolated nucleic acids and vectors of the disclosure have reduced toxicity and/or increased transgene expression relative to previously described SMN-encoding vectors.

公开(公告)号：US20240076692A1

公开(公告)日：2024-03-07

申请号：US18345366

申请日：2023-06-30

Applicant: University of Massachusetts

Inventor： Guangping Gao ,  Hemant Khanna

IPC: C12N15/86 ,  A61K9/00 ,  A61K35/761 ,  A61P27/02 ,  C07K14/47 ,  C12N7/00

CPC classification number: C12N15/86 ,  A61K9/0048 ,  A61K35/761 ,  A61P27/02 ,  C07K14/47 ,  C12N7/00 ,  A61K48/00

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：US20240035046A1

公开(公告)日：2024-02-01

申请号：US18450033

申请日：2023-08-15

Applicant: University of Massachusetts

Inventor： Jun Xie ,  Guangping Gao

IPC: C12N15/86 ,  C12N15/113

CPC classification number: C12N15/86 ,  C12N15/113 ,  C12N2310/141 ,  C12N2740/15043 ,  C12N2740/15052 ,  C12N2750/14143 ,  C12N2750/14152

Abstract: In some aspects, the disclosure relates to methods for improving titer and yield of viral vector production. In some embodiments, the methods comprise transient silencing of transgene expression during packaging of a viral vector.

公开(公告)号：US11882815B2

公开(公告)日：2024-01-30

申请号：US16310381

申请日：2017-06-15

Applicant: University of Massachusetts

Inventor： Jaime Antonio Rivera-Perez ,  Guangping Gao

IPC: A01K67/027 ,  C12N15/864 ,  C12N5/073 ,  C12N15/85 ,  C12N9/22

CPC classification number: A01K67/0275 ,  C12N5/0604 ,  C12N9/22 ,  C12N15/8509 ,  C12N15/8645 ,  A01K2217/075 ,  C12N2015/8527 ,  C12N2750/14143

Abstract: The disclosure, in some aspects, relates to methods and compositions for recombinant adeno-associated virus (rAAV)-mediated delivery of genome editing molecules to a pre-implantation embryo.

公开(公告)号：US20230348914A1

公开(公告)日：2023-11-02

申请号：US17918689

申请日：2021-04-13

Applicant: University of Massachusetts

Inventor： Jun Xie ,  Yi Wang ,  Sha Zhu ,  Guangping Gao

IPC: C12N15/113 ,  C12N15/86 ,  A61K48/00 ,  A61P1/16

CPC classification number: C12N15/1137 ,  C12N15/86 ,  A61K48/005 ,  A61P1/16

Abstract: Aspects of the disclosure relate to isolated nucleic acids encoding one or more inhibitory nucleic acids. In some embodiments, the inhibitory nucleic acids are microRNAs (miRNAs) or artificial microRNAs (amiRNAs). The inhibitory nucleic acids may target one or more genes involved in cytochrome p450 toxicity, for example Slc16a2, Acls5, and Cyb5b. In some embodiments, an inhibitory nucleic acid is a miR-375. The disclosure relates, in some aspects, to methods of reducing cytochrome p450-related toxicity in a cell (e.g., a liver cell) by administering the isolated nucleic acids of the disclosure.

公开(公告)号：US11773410B2

公开(公告)日：2023-10-03

申请号：US16093575

申请日：2017-04-13

Applicant: University of Massachusetts

Inventor： Guangping Gao ,  Dan Wang

IPC: C12N15/90 ,  C12N9/22 ,  C12N15/10 ,  C12N15/11 ,  C12N15/86

CPC classification number: C12N15/907 ,  C12N9/22 ,  C12N15/1024 ,  C12N15/11 ,  C12N15/86 ,  C12N2320/34 ,  C12N2750/14143 ,  C12N2800/80

Abstract: The disclosure in some aspects relates to methods and compositions for repairing mutations (e.g., compound heterozygous mutations) that are widely found in patients having certain diseases (e.g., monogenic recessive diseases). In some aspects, the disclosure provides a method for targeted allelic exchange using recombinant gene editing complex.

公开(公告)号：US20230183711A1

公开(公告)日：2023-06-15

申请号：US17767962

申请日：2020-10-14

Applicant: University of Massachusetts

Inventor： Guangping Gao ,  Dan Wang ,  Jote Bulcha

IPC: C12N15/52 ,  C07K14/005

CPC classification number: C12N15/52 ,  C07K14/005 ,  C12N2750/14122 ,  C12N2750/14143 ,  C12N2750/14152

Abstract: Aspects of the disclosure relate to manufacturing AAV using a stable cell line that expresses the rep gene by engineering tRNA to suppress a mutation introduced to a rep integrated into the genome of the cell line.

公开(公告)号：US20230138766A1

公开(公告)日：2023-05-04

申请号：US17915548

申请日：2021-03-30

Applicant: University of Massachusetts ,  Sichuan University

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

IPC: C12N15/86 ,  A61K9/00 ,  C07K14/005

Abstract: Aspects of the disclosure relate to compositions and methods for delivering a transgene (e.g., a transgene encoding one or more gene products) to a target cell. The disclosure is based, in part, on adeno-associated virus (AAV) capsid protein variants characterized by tropisms for certain cell types (e.g., neurons, muscle cells, bone cells, heart cells, etc.). In some embodiments, recombinant A A Vs (rAAVs) comprising the capsid protein variants (e.g., AAVv66, SEQ ID NO: 1) are more efficiently packaged than rAAVs having certain wild-type AAV capsid proteins. Methods of delivering an rAAV comprising the AAV capsid protein variants are also described by the disclosure.

公开(公告)号：US20220403417A1

公开(公告)日：2022-12-22

申请号：US17778212

申请日：2020-11-19

Applicant: University of Massachusetts

Inventor： Jun Xie ,  Guangping Gao

IPC: C12N15/86 ,  C12N9/12 ,  A61K9/00

Abstract: In some aspects the disclosure provides compositions and methods for promoting expression of functional Thymine Kinase 2 (TK2) protein in a subject. In some embodiments, the disclosure provides methods of treating a subject having TK2 deficiency, for example a subject having mitochondrial DNA depletion syndrome.

公开(公告)号：US20210340539A1

公开(公告)日：2021-11-04

申请号：US17316769

申请日：2021-05-11

Applicant: University of Massachusetts

Inventor： Guangping Gao ,  Jun Xie ,  Phillip D. Zamore

IPC: C12N15/113 ,  A61K31/713 ,  C12N15/11 ,  C12N15/86

Abstract: The present disclosure relates to the field of rAAV delivery of transgenes. In some aspects, the disclosure relates to RNAi. Provided herein are recombinant adeno-associated virus (rAAV) vectors comprising modified ITRs. In some embodiments, the modified ITRs comprise a sequence encoding a shRNA, miRNA, or AmiRNA.