Baylor College of Medicine

University of Houston System

Other

The Texas A&M University System

Texas Heart Institute

Halliburton Company

Genetronics, Inc.

Vgx Pharmaceuticals, Inc.

Drilex Systems, Inc.

Advisys, Inc.

Animatus Biosciences, LLC

Inovio Pharmaceuticals, Inc.

Robert J Schwartz

Ruxandra Draghia-Akli

Bert W O'Malley

Yu Liu

Franco J DeMayo

Xiaopeng Shen

Xuyang Li

Eric M Eastman

Robert Hunt Carpenter

Malcolm K Brenner

Douglas R Kern

Dinakar Iyer

Ruxandra Draghia-Alki

Jeff Nordstrom

Glen King

Jose Francisco Islas

Vladimir N Potaman

Kevin Hahn

David S Chang

James M Briggs

Hua Zhang

Scott R Gilbertson

Steven Bark

James D Tuttle

Robert Fox

Mark Entman

Siyu Xiao

John W Craft

Kevin MacKenzie

King L Chow

Joseph V Hebert

Reza Abbasgholizadeh

Jiang Chang

Lei Wei

Joe Marx

Narasimhaswamy Belaguli

Loss of cardiomyocytes underlies most causes of heart failure, and normal repair processes are inadequate to deal with extensive myocardial damage. The inventors have identified mutations of the N-terminus of serum response factor (SRF)'s MADS box, termed STEMINs, that block cardiac differentiation, but also powerfully activate the stem cell marker genes Nanog and Octomer 4, as well as cyclins, which promotes adult myocyte replication. SRF Stemin mutations are not cardiac-specific, and also propel mammalian fibroblasts into a proliferative state. Thus, STEMINs may be useful for regeneration of all tissue and organ types, by activating partial pluripotency programs and enhancing repair by increased cell replication. Following withdrawal of STEMINs, the cells then return to normal cell identity.

Serum response factor regenerates senescent cells

Compositions and methods for promoting adult mammalian cardiomyocytes processes and systems for enhancing cardiomyocyte regeneration are described. The invention relates to locally administering a therapeutic agent containing a modified messenger RNA for expressing a mutated serum response factor polypeptide and a modified messenger RNA for expressing a mutated YAP polypeptide into diseased heart muscle to promote cardiomyocyte proliferation and cardiac regeneration.

Enhanced cardiomyocyte regeneration

The present disclosure describes peptide inhibitors of Rho-associtated-kinase (ROCK) and their use in treating disorders including heart failure, the leading cause of combined morbidity and mortality in the United States. An inhibitory polypeptide blocks ROCK1 activity in the presence of 1 mM ATP. The binding epitope on ROCK1 was mapped using chemical cross-linking to the Activation Loop, a novel locus identifying a new class of inhibitory drugs. The peptides described will be useful against a number of important diseases such as heart disease, pulmonary hypertension, arterial hypertension, glaucoma management, insulin resistance, kidney disease, hemolytic anemia, stroke, ischemia reperfusion injury, or acute myeloid leukemia.

Rho associated kinase (ROCK) inhibitors and their use in treating disease

The present disclosure describes the role for miR-322(424)/503 in the differentiation of cardiac precursor cells. Thus, the use of these molecules in the programming of resident stem/progenitor cells into cardiomyocytes, both in vitro and in vivo. Such methods find particular use in the treatment of patients post-myocardial infarction to prevent or limit scarring and to promote myocardial repair.

Therapeutic miRNAs for treating heart and skeletal muscle diseases

A method for modulating cell differentiation capabilities using heterologous gene expression. Some embodiments of the invention relate to a method for inducing a cardiac progenitor cell by delivering a reprogramming factor to the cell, wherein the reprogramming factor comprises ETS2 or a combination of ETS2 and Mesp1.

Ets2 and Mesp1 generate cardiac progenitors from fibroblasts

ETS2 and MESP1 generate cardiac progenitors from fibroblasts

The present invention pertains to compositions and methods useful for treating anemia and other effects that are commonly associated in cancer bearing animals. The invention is accomplished by delivering an effective amount of a nucleic acid expression construct that encodes a GHRH or functional biological equivalent thereof into a tissue of an animal and allowing expression of the encoded gene in the animal.

Gene therapy expression of GHRH for increasing RBC count in subjects

The invention concerns making and evaluating synthetic regulatory regions for controlling gene expression. The invention features a method for identifying transcription factor binding sites and a method for evaluating the regulatory functions of synthetic regulatory regions.

Synthetic cell-or tissue-specific transcriptional regulatory regions

The present invention is directed to generating a smooth muscle cell from another cell, such as a fibroblast, by delivering to the cell serum response factor, a CRP, and a GATA. In specific embodiments, the methods are utilized to generate vascular tissue and/or to repair vascular tissue.

Smooth muscle cell differentiation with CRP, SRF and GATA factors

The present invention is directed to the cleavage of serum response factor as it relates to cardiac disease. In specific embodiments, failing cardiac tissue is diagnosed in tissues comprising elevated cleavage of serum response factor. In further specific embodiments, heart failure is associated with cardiac myocyte apoptosis as a result of an increase in cleaved serum response factor, particularly by caspases.

Cleaved serum response factor in cardiac diagnosis and therapy

A method for decreasing the body fat proportion, increasing lean body mass, increasing bone density, or improving the rate of bone healing, or all, of a subject. Embodiments of the invention include delivering a heterologous nucleic acid sequence encoding GHRH or functional biological equivalent thereof into the cells of the subject and allowing expression of the encoded gene to occur while the modified cells are within the subject.

Composition and method to alter lean body mass and bone properties in a subject

The present invention pertains to compositions and methods for plasmid-mediated supplementation. The compositions and method are useful for retarding the growth of the tumor, and retarding cachexia, wasting, anemia and other effects that are commonly associated in cancer bearing animals. Overall, the embodiments of the invention can be accomplished by delivering an effective amount of a nucleic acid expression construct that encodes a GHRH or functional biological equivalent thereof into a tissue of an animal and allowing expression of the encoded. gene in the animal. For example, when such a nucleic acid sequence is delivered into the specific cells of the tissue specific constitutive expression is achieved.

Treating anemia in subjects by administration of plasmids encoding growth hormone releasing hormone

Inadequate growth due to deficiencies in growth hormone (GR), growth hormone releasing hormone (GHRH), or genetic diseases can be ameliorated utilizing recombinant protein therapy with a novel GHRH analog having a sequence (SEQ ID NO:1). Also included is (1) a method of treating growth hormone-related deficiencies associated with the growth hormone pathway; (2) a method for treating growth hormone-related deficiencies associated with genetic disease; (3) a method to improve growth performance in an animal; (4) a method of treating an animal having a growth deficiency disease; (5) a method of increasing the efficiency of an animal used for food; and (6) a method to enhance growth in an animal.

Polynucleotides encoding a super-active porcine growth hormone releasing hormone analog

Growing community of inventors

Houston, TX, United States of America

Robert J Schwartz