公开(公告)号：US12077562B2

公开(公告)日：2024-09-03

申请号：US17930166

申请日：2022-09-07

Applicant: University of Massachusetts ,  The Johns Hopkins University ,  Kennedy Krieger Institute, Inc.

Inventor： Miguel Sena Esteves ,  Sourav Roy Choudhury ,  Kathryn Rae Wagner ,  Jennifer Gifford Green ,  Ana Rita Batista

IPC: C07K14/01 ,  C07K14/005 ,  C07K14/015 ,  C07K14/47 ,  C12N7/00 ,  A61K38/00

CPC classification number: C07K14/01 ,  C12N7/00 ,  A61K38/00 ,  C12N2310/141 ,  C12N2750/14122

Abstract: The disclosure relates, in some aspects, to adeno-associated virus capsid proteins isolated from an in vivo library and recombinant adeno-associated viruses (rAAVs) comprising the same. In some aspects, the disclosure relates to isolated nucleic acids encoding AAV capsid proteins isolated from an in vivo library. In some embodiments, rAAVs and compositions described by the disclosure are useful for delivery of one or more transgenes to the muscle-tissue of a subject.

公开(公告)号：US20240139340A1

公开(公告)日：2024-05-02

申请号：US18490841

申请日：2023-10-20

Applicant: University of Massachusetts

Inventor： Miguel Sena Esteves ,  Ana Rita Batista ,  Sourav Roy Choudhury

IPC: A61K48/00 ,  A61K9/00 ,  A61K31/351 ,  A61K31/4706 ,  A61K31/5415 ,  A61K31/7016 ,  A61K38/17 ,  A61K47/42 ,  A61K47/62 ,  A61K47/64 ,  C07K14/775 ,  C12N15/63 ,  C12N15/64 ,  C12N15/79 ,  C12N15/86

CPC classification number: A61K48/0008 ,  A61K9/0085 ,  A61K31/351 ,  A61K31/4706 ,  A61K31/5415 ,  A61K31/7016 ,  A61K38/1709 ,  A61K47/42 ,  A61K47/62 ,  A61K47/6455 ,  C07K14/775 ,  C12N15/63 ,  C12N15/64 ,  C12N15/79 ,  C12N15/86 ,  C07K5/0808 ,  C07K2319/00 ,  C07K2319/33

Abstract: The disclosure relates, in some aspects, to compositions and methods for enhanced delivery of a transgene to the central nervous system (CNS) of a subject. In some embodiments, the transgene is delivered by recombinant AAV (rAAV). In some embodiments, the method of enhancing transgene delivery comprises administering a blood brain barrier (BBB)-crossing molecule (e.g., K16ApoE) and an rAAV comprising a transgene to a subject.

公开(公告)号：US20220090135A1

公开(公告)日：2022-03-24

申请号：US17483115

申请日：2021-09-23

Applicant: University of Massachusetts

Inventor： Miguel Sena Esteves ,  Anshuman Singh

IPC: C12N15/86 ,  C07K14/47 ,  A61P35/00

Abstract: Aspects of the disclosure relate to compositions and methods of treating certain genetic disease (e.g., Neurofibromatosis type I) by delivering functional neurofibromin 1 (NF1) protein (e.g., mini-NF1 protein and/or full-length NF1 protein) to target cell (e.g., cells and/or tissue of a subject). The disclosure is based, in part, on isolated nucleic acids (e.g., rAAV vectors) and rAAVs engineered to express a functional NF1 protein (e.g., mini-NF1 protein and/or full-length NF1 protein) or variants thereof.

公开(公告)号：US12091659B2

公开(公告)日：2024-09-17

申请号：US16879914

申请日：2020-05-21

Applicant: University of Massachusetts

Inventor： Miguel Sena Esteves ,  Sourav Roy Choudhury

IPC: C12N15/10 ,  C07K14/005 ,  C40B40/08

CPC classification number: C12N15/1065 ,  C07K14/005 ,  C40B40/08 ,  C12N2750/14122 ,  C12N2750/14143 ,  C12N2750/14151 ,  C12N2750/14171

Abstract: Aspects of the disclosure relate to barcoded chimeric adeno-associated virus (AAV) capsid libraries, chimeric capsids and related recombinant AAVs (rAAVs) identified using the libraries. Specifically, the chimeric AAV capsid libraries comprise a plurality of nucleic adds encoding AAV capsid proteins, wherein each nucleic acid (i) encodes a unique AAV capsid protein having distinct polypeptide regions of greater than six amino acids in length that are derived from at least two different AAV serotypes, and (ii) comprises a unique barcode sequence. Further disclosed are methods of preparing an AAV library and identifying AAV capsids tropic for a target tissue.

公开(公告)号：US20230279405A1

公开(公告)日：2023-09-07

申请号：US18017479

申请日：2021-07-23

Applicant: University of Massachusetts

Inventor： Miguel Sena Esteves ,  Scot A. Wolfe

IPC: C12N15/62 ,  C12N15/86 ,  C12N15/10

CPC classification number: C12N15/62 ,  C12N15/86 ,  C12N15/1034 ,  C07K2319/01 ,  C12N2750/14143 ,  C12N2830/008

Abstract: In some aspects, the disclosure relates to recombinant adeno-associated viruses (rAAVs) comprising a nucleic acid encoding a fusion protein comprising a DNA-binding domain and a transcriptional regulator domain and methods of using the same. In some embodiments, expression of the fusion protein results in modified expression of a target gene in a cell.

公开(公告)号：US11472848B2

公开(公告)日：2022-10-18

申请号：US17050475

申请日：2019-04-26

Applicant: University of Massachusetts ,  The Johns Hopkins University ,  Kennedy Krieger Institute, Inc.

Inventor： Miguel Sena Esteves ,  Sourav Roy Choudhury ,  Kathryn Rae Wagner ,  Jennifer Gifford Green ,  Ana Rita Batista

IPC: C12N15/86 ,  A61K48/00 ,  C12N15/113 ,  C12N7/00 ,  C07K14/005 ,  C07K14/01 ,  A61K38/00

Abstract: The disclosure relates, in some aspects, to adeno-associated vims capsid proteins isolated from an in vivo library and recombinant adeno-associated viruses (rAAVs) comprising the same. In some aspects, the disclosure relates to isolated nucleic acids encoding AAV capsid proteins isolated from an in vivo library. In some embodiments, rAAVs and compositions described by the disclosure are useful for delivery of one or more transgenes to the muscle-tissue of a subject.

公开(公告)号：US20210324044A1

公开(公告)日：2021-10-21

申请号：US17237095

申请日：2021-04-22

Applicant: University of Massachusetts

Inventor： Miguel Sena Esteves ,  Sourav Roy Choudhury

IPC: C07K14/775 ,  C07K7/00 ,  C07K14/00 ,  C07K14/005 ,  C12N15/86 ,  A61K48/00 ,  C07K7/04 ,  C07K14/075 ,  C07K19/00 ,  C12N15/79

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：US20250034555A1

公开(公告)日：2025-01-30

申请号：US18804218

申请日：2024-08-14

Applicant: University of Massachusetts

Inventor： Miguel Sena Esteves ,  Sourav Roy Choudhury

IPC: C12N15/10 ,  C07K14/005 ,  C40B40/08

Abstract: Aspects of the disclosure relate to barcoded chimeric adeno-associated virus (AAV) capsid libraries, chimeric capsids and related recombinant AAVs (rAAVs) identified using the libraries. Specifically, the chimeric AAV capsid libraries comprise a plurality of nucleic adds encoding AAV capsid proteins, wherein each nucleic acid (i) encodes a unique AAV capsid protein having distinct polypeptide regions of greater than six amino acids in length that are derived from at least two different AAV serotypes, and (ii) comprises a unique barcode sequence. Further disclosed are methods of preparing an AAV library and identifying AAV capsids tropic for a target tissue.

公开(公告)号：US20230067741A1

公开(公告)日：2023-03-02

申请号：US17930166

申请日：2022-09-07

Applicant: University of Massachusetts ,  The Johns Hopkins University ,  Kennedy Krieger Institute, Inc.

Inventor： Miguel Sena Esteves ,  Sourav Roy Choudhury ,  Kathryn Rae Wagner ,  Jennifer Gifford Green ,  Ana Rita Batista

IPC: C07K14/01 ,  C12N7/00

Abstract: The disclosure relates, in some aspects, to adeno-associated virus capsid proteins isolated from an in vivo library and recombinant adeno-associated viruses (rAAVs) comprising the same. In some aspects, the disclosure relates to isolated nucleic acids encoding AAV capsid proteins isolated from an in vivo library. In some embodiments, rAAVs and compositions described by the disclosure are useful for delivery of one or more transgenes to the muscle-tissue of a subject.

公开(公告)号：US20210381004A1

公开(公告)日：2021-12-09

申请号：US17282421

申请日：2019-10-04

Applicant: University of Massachusetts

Inventor： Miguel Sena Esteves

IPC: C12N15/86 ,  C12N9/24 ,  A61P3/00

Abstract: Aspects of the disclosure relate to compositions and methods for the treatment of lysosomal storage disorders, such as GM1 gangliosidosis, Tay Sachs disease, and Sandhoff disease. In some embodiments, the compositions comprise viral vectors encoding beta-galactosidase. In some embodiments, the compositions comprise viral vectors encoding beta-hexosaminidase subunits (e.g. HEXA, HEXB, or combinations thereof).