公开(公告)号：US10130679B2

公开(公告)日：2018-11-20

申请号：US15074714

申请日：2016-03-18

Applicant: University of Massachusetts

Inventor： Michael R. Green ,  Guangping Gao ,  Manas Kumar Santra ,  Sanchita Bhatnagar

IPC: A61K38/17 ,  A61K38/16 ,  A61K48/00 ,  A61K35/12 ,  C12N9/08

Abstract: Methods of treating a tumor in a subject include identifying a subject having, at risk for, or suspected of having a tumor, and administering to the subject an effective amount of an SRPX.

公开(公告)号：US20180179501A9

公开(公告)日：2018-06-28

申请号：US15550452

申请日：2016-02-12

Applicant: University of Massachusetts

Inventor： Guangping Gao ,  Phillip D. Zamore ,  Dan Wang

IPC: C12N9/22 ,  C07K14/005 ,  C12N7/00 ,  C12N15/11 ,  C12N15/90 ,  A61K48/00

CPC classification number: C12N9/22 ,  A61K38/00 ,  A61K48/005 ,  C07K14/005 ,  C07K2319/735 ,  C12N7/00 ,  C12N15/11 ,  C12N15/907 ,  C12N2310/20 ,  C12N2750/14121 ,  C12N2750/14122 ,  C12N2750/14142 ,  C12N2750/14143

Abstract: The disclosure in some aspects relates to recombinant adeno-associated viruses having nuclease grafted to one or more capsid proteins. In some aspects, the disclosure relates to isolated AAV capsid proteins having terminally grafted nucleases and isolated nucleic acids encoding the same. Recent approaches to delivering nucleases to cells for gene editing have focused on delivering of expression vectors engineered to express the nucleases in target cells. However, these approaches have proved to be problematic in many instances due to genotoxicity resulting from to prolonged expression of gene editing system in vivo. To prevent such off-target genotoxicity due to prolonged presence of a gene editing system, several studies explored delivery of mRNA or protein instead of delivering the gene coding for the nucleases in cell culture.

公开(公告)号：US20180037877A1

公开(公告)日：2018-02-08

申请号：US15550452

申请日：2016-02-12

Applicant: University of Massachusetts

Inventor： Guangping Gao ,  Phillip D. Zamore ,  Dan Wang

IPC: C12N9/22 ,  A61K48/00 ,  C12N15/11 ,  C12N15/90 ,  C07K14/005 ,  C12N7/00

CPC classification number: C12N9/22 ,  A61K38/00 ,  A61K48/005 ,  C07K14/005 ,  C07K2319/735 ,  C12N7/00 ,  C12N15/11 ,  C12N15/907 ,  C12N2310/20 ,  C12N2750/14121 ,  C12N2750/14122 ,  C12N2750/14142 ,  C12N2750/14143

Abstract: The disclosure in some aspects relates to recombinant adeno-associated viruses having nuclease grafted to one or more capsid proteins. In some aspects, the disclosure relates to isolated AAV capsid proteins having terminally grafted nucleases and isolated nucleic acids encoding the same. Recent approaches to delivering nucleases to cells for gene editing have focused on delivering of expression vectors engineered to express the nucleases in target cells. However, these approaches have proved to be problematic in many instances due to genotoxicity resulting from to prolonged expression of gene editing system in vivo. To prevent such off-target genotoxicity due to prolonged presence of a gene editing system, several studies explored delivery of mRNA or protein instead of delivering the gene coding for the nucleases in cell culture.

公开(公告)号：US20170191039A1

公开(公告)日：2017-07-06

申请号：US15120294

申请日：2015-02-19

Applicant: University of Massachusetts

Inventor： Guangping Gao ,  Li Zhong

IPC: C12N7/00 ,  A61K38/17 ,  A61K48/00 ,  C12N15/86 ,  C12N15/113

CPC classification number: C12N7/00 ,  A61K38/1709 ,  A61K48/0058 ,  C12N15/113 ,  C12N15/86 ,  C12N2310/141 ,  C12N2710/10332 ,  C12N2710/10342 ,  C12N2750/14122 ,  C12N2750/14143 ,  C12N2750/14171

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

公开(公告)号：US20170166927A1

公开(公告)日：2017-06-15

申请号：US15423720

申请日：2017-02-03

Applicant: University of Massachusetts

Inventor： Guangping Gao ,  Phillip D. Zamore

IPC: C12N15/86 ,  A61K48/00 ,  A61K9/00

CPC classification number: A61K48/0008 ,  A01K67/0275 ,  A01K2207/05 ,  A01K2217/058 ,  A01K2227/105 ,  A01K2267/03 ,  A01K2267/0331 ,  A61K9/0019 ,  A61K38/00 ,  A61K48/0058 ,  C12N7/00 ,  C12N15/111 ,  C12N15/113 ,  C12N15/8509 ,  C12N15/86 ,  C12N2015/8527 ,  C12N2310/13 ,  C12N2310/141 ,  C12N2320/32 ,  C12N2330/51 ,  C12N2710/10342 ,  C12N2750/14143 ,  C12N2750/14145 ,  C12N2820/002 ,  C12N2840/007 ,  C12N2840/102

Abstract: The invention in some aspects relates to isolated nucleic acids, compositions, and kits useful for identifying adeno-associated viruses in cells. In some aspects, the invention provides kits and methods for producing somatic transgenic animal models using recombinant AAV (rAAV) to an animal having at least one transgene that expresses a small interfering nucleic acid or at least one binding site for a miRNA.

公开(公告)号：US20170145439A1

公开(公告)日：2017-05-25

申请号：US15367708

申请日：2016-12-02

Applicant: University of Massachusetts

Inventor： Guangping Gao ,  Jun Xie

IPC: C12N15/86 ,  C12N15/113 ,  C12N7/00

Abstract: Some aspects of this invention provide nucleic acid constructs for transgene expression. Some aspects of this invention provide multicistronic nucleic acid constructs, for example, comprising an expression cassette encoding a hairpin RNA and a reporter expression cassette. Some aspects of this invention provide nucleic acid constructs comprising two or more self-complementary nucleic acid sequences, for example, hairpin RNA encoding nucleic acid sequences and AAV inverse terminal repeats. Methods for the use of the constructs in therapy and research are also provided.

公开(公告)号：US12054715B2

公开(公告)日：2024-08-06

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 ,  C12Q1/68

CPC classification number: C12N15/113 ,  A61K31/713 ,  C12N15/111 ,  C12N15/86 ,  C12N2310/11 ,  C12N2310/141 ,  C12N2310/531 ,  C12N2330/51 ,  C12N2750/14143 ,  C12N2750/14171

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.

公开(公告)号：US11926842B2

公开(公告)日：2024-03-12

申请号：US17590337

申请日：2022-02-01

Applicant: University of Massachusetts

Inventor： Guangping Gao ,  Phillip Tai ,  Elisabet C. Mandon ,  Jianzhong Ai

IPC: C12N15/86

CPC classification number: C12N15/86 ,  C12N2750/14143 ,  C12N2750/14171

Abstract: In some aspects, the disclosure provides recombinant AAV and nucleic acid constructs having novel inverted terminal repeats (ITRs), cap, and/or rep genes. In some aspects, the disclosure relates to gene transfer methods using rAAVs described herein.

公开(公告)号：US20240002844A1

公开(公告)日：2024-01-04

申请号：US18021901

申请日：2021-08-18

Applicant: University of Massachusetts

Inventor： Jae-Hyuck Shim ,  Guangping Gao ,  Jun Xie ,  Yeon-Suk Yang

IPC: C12N15/113 ,  C12N15/86 ,  A61P29/00 ,  A61P19/02

CPC classification number: C12N15/113 ,  C12N15/86 ,  C12N2750/14143 ,  A61P19/02 ,  C12N2310/141 ,  A61P29/00

Abstract: Aspects of the disclosure relate to compositions and methods for reding inflammation and/or inhibiting bone loss (e.g., bone loss induced by inflammation). In some embodiments, the disclosure provides isolated nucleic acids and expression constructs (e.g., rAAVs, etc.) that encode one or more of the following transgenes: inhibitory nucleic acids targeting Schnurri 3 (SHN3), inhibitory nucleic acids targeting Cathepsin K (CTSK), inhibitory nucleic acids targeting sclerostin (SOST), inhibitory nucleic acids targeting receptor activator of NF-κβ (RANK), inhibitory nucleic acids targeting receptor activator of NF-κβ ligand (RANKL), soluble TNF-α Receptor 2 (sTNFR2), and soluble IL-1 Receptor Antagonist (sIL1Rα). In some embodiments, compositions described by the disclosure are useful for treating diseases associated with inflammation, for example rheumatoid arthritis (RA).

公开(公告)号：US20230346978A1

公开(公告)日：2023-11-02

申请号：US17918714

申请日：2021-04-13

Applicant: University of Massachusetts

Inventor： Dan Wang ,  Guangping Gao ,  Jiaming Wang

IPC: A61K48/00 ,  C12N15/11 ,  C12N9/22 ,  C12N9/78 ,  C12N15/86 ,  A61P43/00

CPC classification number: A61K48/0066 ,  C12N15/11 ,  C12N9/22 ,  C12N9/78 ,  C12Y305/04004 ,  C12N15/86 ,  A61P43/00 ,  C12N2310/20 ,  C12N2750/14143

Abstract: Aspects of the disclosure relate to compositions (e.g., isolated nucleic acids, rAAV vectors, rAAVs, etc.) and methods for gene editing. The disclosure is based, in part, on isolated nucleic acids encoding combinations of gene editing proteins (e.g., Cas proteins) and base editors (e.g., Adenosine Deaminase Acting on RNA deaminase domains) with certain regulatory sequences that are amenable to packaging in recombinant adeno-associated viruses (rAAVs). In some embodiments, compositions described by the disclosure are useful for treating certain diseases in a subject in need thereof.