公开(公告)号：US12084658B2

公开(公告)日：2024-09-10

申请号：US17500410

申请日：2021-10-13

Applicant: RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL

Inventor： Scott Quenton Harper ,  Nicolas Sebastien Wein

IPC: C12N15/113 ,  A61P21/00 ,  C12N15/864 ,  C12Q1/68

CPC classification number: C12N15/113 ,  A61P21/00 ,  C12N15/8645 ,  C12Q1/68 ,  C12N2310/11 ,  C12N2320/32 ,  C12N2320/33 ,  C12N2330/51

Abstract: The present invention relates to methods for shifting the splicing profile of the DUX4 gene, a double homeobox gene on human chromosome 4q35. Recombinant adeno-associated viruses of the invention deliver DNAs encoding U7-based small nuclear RNAs to induce DUX4 exon-skipping and the expression of shortened forms of DUX4. The methods have application in the treatment of muscular dystrophies such as facioscapulohumeral muscular dystrophy.

公开(公告)号：US20230077409A1

公开(公告)日：2023-03-16

申请号：US17729751

申请日：2022-04-26

Applicant: RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL

Inventor： Scott Quenton Harper

IPC: C12N15/113 ,  C07H21/02 ,  A61P21/00 ,  A61K9/00 ,  C12N7/00

Abstract: The present invention relates to a tissue-specific promoter system for expressing microRNA (miRNA) for RNA interference-based methods of gene therapy. In these systems, the miRNA will inhibit gene expression or replace natural miRNA expression using microRNA.

公开(公告)号：US20190024083A1

公开(公告)日：2019-01-24

申请号：US16079426

申请日：2017-02-24

Applicant: RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL

Inventor： Scott Quenton Harper

IPC: C12N15/113 ,  C12N15/864 ,  A61P21/00

Abstract: The present invention relates to methods for shifting the splicing profile of the DUX4 gene, a double homeobox gene on human chromosome 4q35. Recombinant adeno-associated viruses of the invention deliver DNAs encoding U7-based small nuclear RNAs to induce DUX4 exon-skipping and the expression of shortened forms of DUX4. The methods have application in the treatment of muscular dystrophies such as facioscapulohumeral muscular dystrophy.

公开(公告)号：US20190136235A1

公开(公告)日：2019-05-09

申请号：US16089860

申请日：2017-03-31

Applicant: RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL

Inventor： Scott Quenton Harper

IPC: C12N15/113 ,  A61P21/00 ,  A61K9/00 ,  C12N7/00 ,  A61K48/00

Abstract: The present invention relates to a tissue-specific promoter system for expressing microRNA (miRNA) for RNA interference-based methods of gene therapy. In these systems, the miRNA will inhibit gene expression or replace natural miRNA expression using microRNA.

公开(公告)号：US20240318172A1

公开(公告)日：2024-09-26

申请号：US18038900

申请日：2021-11-30

Applicant: RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL ,  The Cyprus Foundation for Muscular Dystrophy Research D/B/A The Cyprus Institute of Neurology...

Inventor： Scott Quenton Harper ,  Kleopas Kleopa ,  Marina Stavrou

IPC: C12N15/113 ,  A61K31/7088 ,  A61K48/00 ,  A61P21/00 ,  C12N15/86

CPC classification number: C12N15/113 ,  A61K31/7088 ,  A61K48/005 ,  A61P21/00 ,  C12N15/86 ,  C12N2310/11 ,  C12N2310/141 ,  C12N2750/14143

Abstract: RNA interference-based methods and products for inhibiting the expression of a peripheral myelin protein-22 gene are provided. RNAs that inhibit the peripheral myelin protein-22 gene are provided as well as DMAs encoding the RNAs. Delivery vehicles such as recombinant adeno-associated viruses deliver DMAs encoding RNAs that inhibit the peripheral myelin protein-22 gene. The methods treat Charcot-Marie-Tooth Disease such as Charcot-Marie-Tooth Disease Type 1 A (CMT1A).

公开(公告)号：US20240026356A1

公开(公告)日：2024-01-25

申请号：US18038878

申请日：2021-11-30

Applicant: RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL

Inventor： Scott Quenton Harper ,  Afrooz Rashnonejad ,  Nicolas Sebastien Wein

IPC: C12N15/113 ,  C12N15/86 ,  A61P21/00

CPC classification number: C12N15/113 ,  C12N15/86 ,  A61P21/00 ,  C12N2310/11 ,  C12N2750/14143

Abstract: Disclosed herein are products, methods, and uses for treating, ameliorating, udaying the progression of, and/or preventing a muscular dystrophy or a cancer including, but not limited to, facioscapulohumeral muscular dystrophy (FSHD) or a sarcoma. More particularly, disclosed herein are RNA interference-based products, methods, and uses for inhibiting or downregulating the expression of double homeobox 4 (DUX4). Even more particularly, the disclosure provides nucleic acids comprising U7 DUX4 antisense sequences for inhibiting or downregulating the expression of DUX4 and methods of using said antisense sequences to inhibit or downregulate DUX4 expression in cells and/or in cells of a subject having a muscular dystrophy or a cancer including, but not limited to, FSHD or a cancer.

公开(公告)号：US20210324417A1

公开(公告)日：2021-10-21

申请号：US17271377

申请日：2019-08-29

Applicant: RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL ,  THE JACKSON LABORATORY

Inventor： Scott Quenton Harper ,  Robert W. Burgess

IPC: C12N15/86 ,  C12N15/113 ,  C12N9/00 ,  A61K38/53 ,  A61P25/00

Abstract: RNA interference-based methods and products for inhibiting the expression of mutant Glycyl-tRNA Synthetase (GARS) genes are provided. Delivery vehicles such as recombinant adeno-associated viruses deliver DMAs encoding GARS microRNAs, as well as a replacement GARS gene that is resistant to knock down by the microRNAs. The methods have application in the treatment of N diseases or disorders associated with mutant GARS including, but not limited to, Charcot-Marie-Tooth Disease Type 2D (CMT2D).

公开(公告)号：US20200248179A1

公开(公告)日：2020-08-06

申请号：US16651814

申请日：2018-10-02

Applicant: RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL

Inventor： Scott Quenton Harper

IPC: C12N15/113 ,  C12N15/86 ,  C12N7/00 ,  A61K35/76 ,  A61K9/00

Abstract: The present disclosure relates to a tissue-specific promoter system for expressing microRNA (miRNA) for RNA interference-based methods of gene therapy. In these systems, the miRNA will inhibit gene expression or replace natural miRNA expression using microRNA.

公开(公告)号：US20250019697A1

公开(公告)日：2025-01-16

申请号：US18444111

申请日：2024-02-16

Applicant: Research Institute at Nationwide Children's Hospital

Inventor： Scott Quenton Harper

IPC: C12N15/113 ,  A61K9/00 ,  A61K48/00 ,  A61P21/00 ,  C07H21/02 ,  C12N7/00 ,  C12Q1/70

Abstract: The present invention relates to a tissue-specific promoter system for expressing microRNA (miRNA) for RNA interference-based methods of gene therapy. In these systems, the miRNA will inhibit gene expression or replace natural miRNA expression using microRNA.

公开(公告)号：US20220267768A1

公开(公告)日：2022-08-25

申请号：US17500410

申请日：2021-10-13

Applicant: RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL

Inventor： Scott Quenton Harper ,  Nicolas Sebastien Wein

IPC: C12N15/113 ,  C12Q1/68 ,  A61P21/00 ,  C12N15/864

Abstract: The present invention relates to methods for shifting the splicing profile of the DUX4 gene, a double homeobox gene on human chromosome 4q35. Recombinant adeno-associated viruses of the invention deliver DNAs encoding U7-based small nucle-ar RNAs to induce DUX4 exon- skipping and the expression of shortened forms of DUX4. The methods have application in the treatment of muscular dystrophies such as facioscapulohumeral muscular dystrophy.