University of Missouri

University of Iowa Research Foundation

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Dongsheng Duan

Yongping Yue

John F Engelhardt

Yi Lai

Junling Zhao

Gang Yao

Yuanbo Wang

Ziying Yan

Arkasubhra Ghosh

Chady Hakim

Nalinda B Wasala

Synthetic nucleic acids encoding mini and microdystrophin genes comprising the membrane binding motifs or domains of the R10-R11-R12 region are provided. Also provided are vectors, host cells, and related methods of using the same to treat a subject suffering from Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD) or X-linked dilated cardiomyopathy (XLDC), or for ameliorating one or more adverse effects of DMD, BMD, or XLDC. Also provided are a fusion protein comprising a nNOS binding domain of dystrophin R16-R17 that is operably linked to a syntrophin PDZ domain and synthetic nucleic acids comprising the same that can be used to treat subjects with diseases characterized by loss of sarcolemmal neuronal nitric oxide synthase (nNOS) activity.

Dystrophin R16/R17 syntrophin PDZ fusion proteins

Disclosed herein are methods for systemically editing a gene in a subject and for systemically treating a genetic condition in a subject using a dual-vector CRISPR-Cas therapy. The methods comprise administering to the subject, via systemic administration, a gene editing AAV vector encoding a CRISPR effector protein (e.g., a Cas protein) and a targeting AAV vector providing one or more gRNAs targeted to the gene. In the methods, the ratio of the targeting AAV vector to the gene editing vector is greater than or equal to 2. Also provided are dual-vector systems for editing a gene or treating a genetic disease in a subject.

CRISPR therapy

High-resolution 3D optical polarization tractography (OPT) images of the internal fiber structure of a target tissue. Manipulation of dual-angle imaging data of the fiber orientation inside a target tissue leads to the determination of 3D imaging properties of the target tissue, allowing transmission of the 3D image properties of the target tissue to an OPT processor to produce high-resolution 3D images.

Optical polarization tractography systems, methods and devices

Modified dystrophin proteins

According to the embodiments described herein, a series of biological materials for treatment/therapy of DMD and/or BMD through the recovery of sarcolemmal nNOS is provided. The biological material comprises the complete dystrophin repeats R16 and R17 or certain domains, sections, or fragments of the dystrophin repeats R16 and R17. In some aspects, such domains, sections, or fragments may be selected from sequence motifs including dystrophin R17 &#x3b1;1 helix, &#x3b1;2 and &#x3b1;3 helices of both R16 and R17, or a combination thereof.

Microdystrophin peptides and methods for treating muscular dystrophy using the same

Optical polarization tractography methods

Agents and methods to alter rAAV transduction are provided.

Compounds and methods to enhance rAAV transduction

Hybrid adeno-associated virus (AAV) vector systems able to efficiently express therapeutic target genes larger than may be carried in a single AAV vector are provided, wherein a highly recombinogenic foreign DNA sequence is incorporated into two or more ITR-mediated AAV vectors. In one aspect of one embodiment, the novel hybrid AAV vector system is a hybrid dual AAV (hdAAV) vector system. In another aspect of one embodiment, the novel hybrid AAV vector system is a hybrid tri AAV (htAAV) vector system. A method of treating a clinical disease caused at least in part by a defective gene is provided, and comprises (1) providing a hybrid AAV vector system capable of expressing a therapeutic target gene, wherein the therapeutic target gene is capable of replacing, restoring or counteracting the effects of the defective gene; and (2) administering a therapeutic amount of said vector system to a subject wherein said therapeutic target gene is expressed at levels having a therapeutic effect.

Hybrid-AAV vectors to deliver large gene expression cassette

The present invention provides novel dystrophin mini/micro-genes that retain the essential biological functions of a full-length dystrophin gene. More particularly, the present invention provides to a series of synthetic mini/micro-dystrophin genes capable of restoring neuronal nitric oxide synthase (nNOS) to the sarcolemma. A method as well as a pharmaceutical composition for treatment of Duchenne Muscular Dystrophy (DMD), Becker Muscular Dystrophy (BMD), and X-linked Dilated Cardiomyopathy (XLDC) are also provided.

Synthetic mini/micro-dystrophin genes to restore nNOS to the sarcolemma

The invention provides an isolated and purified DNA molecule comprising at least one DNA segment, a biologically active subunit or variant thereof, of a circular intermediate of adeno-associated virus, which DNA segment confers increased episomal stability, persistence or abundance of the isolated DNA molecule in a host cell. The invention also provides a composition comprising at least two adeno-associated virus vectors.

Adeno-associated virus vectors

Adeno-associated virus vectors and uses thereof

Agents and methods to alter rAAV transduction, including agents and methods to enhance rAAV transduction, are provided. For instance, the invention provides methods to identify agents that enhance AAV transduction after viral binding to the cell membrane and before second strand synthesis.

Growing community of inventors

Columbia, MO, United States of America

Dongsheng Duan