Leland Stanford Junior University

Duke University

The Brigham and Women's Hospital, Inc.

Other

Victor J Dzau

Gary H Gibbons

Maria Mirotsou

John P Cooke

Michael J Mann

Tilanthi Jayawardena

Richard E Pratt

Frank P Diet

Daniel P Griese

Afshin Ehsan

Conrad P Hodgkinson

Ryuichi Morishita

Bruce A Sullenger

Jaewoo Lee

Yasufumi Kaneda

Heiko Von Der Leyen

Giorgio Dell'Acqua

Lawrence H Cohn

Umer Sayeed-Shah

Masahi Mukoyama

Jian Guo

Mirotsou Maria

Maria Miratsou

Arjun Deb

The invention provides a method of promoting reprogramming of a cardiac fibroblast into a cardiomyocyte by contacting the cardiac fibroblast with an isolated polynucleotide molecule comprising at least two functional miRNA sequences using a multicistronic expression system for reprogramming of fibroblasts into functional mature cardiomyocytes.

Multicistronic miRNA delivery for cardiac reprogramming

A method for promoting conversion of cells into cardiomyocytic tissue is carried out by contacting fibrotic tissue (e.g., scar tissue) with a microRNA oligonucleotide or combination of microRNA oligonucleotides. The methods lead to direct reprogramming of fibroblasts to cardiomyocytes or cardiomyoblasts.

Direct reprogramming of cells to cardiac myocyte fate

Disclosed herein are compositions and methods for cellular reprogramming. The compositions comprise one or more miRs and an activator of NF&#x3ba;B. Also provided are methods for enhancing or upregulating cardiomyocyte maturation in a cell or a subject and methods for inhibiting or downregulating cardiomyocyte maturation.

Compositions and methods for cellular reprogramming

A method for promoting the reprogramming of a non-cardiomyocytic cell or tissue into cardiomyocytic cell or tissue comprising is carried out by contacting a non-cardiomyocytic cell or tissue with a modulator of histone methyltransferase activity or expression.

Inhibition of histone methyltransferase for cardiac reprogramming

A purified paracrine factor of a mesenchymal stem cell, such as a Secreted frizzled related protein (Sfrp) is useful to reduce cell death and/or tissue injury associated with ischemic conditions.

Method of reducing cell death by administering a paracrine factor derived from a mesenchymal stem cell

A purified paracrine factor of a mesenchymal stem cell, such as a Secreted frizzled related protein (Sfrp) is useful to reduce cell death an/or tissue injury associated with ischemic conditions.

Method of reducing cell death by administering a nucleic acid encoding a paracrine factor of a mesenchymal stem cell

Method of reducing cell death by administering a paracrine factor of a mesenchymal stem cell

A purified paracrine factor of a mesenchymal stem cell, such as a Secreted frizzled related protein (Sfrp) is useful to reduce cell death an/or tissue injury associated with ischemic condtions.

Method of reducing cell death by administering a Sfrp polypeptide

Method of enhancing cardiac tissue repair by administering a SFRP polypeptide

The invention provides for the use of oligodeoxynucleotide decoys for the prophylactic or therapeutic treatment of diseases associated with the binding of endogenous transcription factors to genes involved in cell growth, differentiation and signalling or to viral genes. By inhibiting endogenous trans-activating factors from binding transcription regulatory regions, the decoys modulate gene expression and thereby regulating pathological processes including inflammation, intimal hyperplasia, angiogenesis, neoplasia, immune responses and viral infection. The decoys are administered in amounts and under conditions whereby binding of the endogenous transcription factor to the endogenous gene is effectively competitively inhibited without significant host toxicity. The subject compositions comprise the decoy molecules in a context which provides for pharmacokinetics sufficient for effective therapeutic use.

Therapeutic use of cis-element decoys in vivo

Therapeutic use of CIS-element decoys in vivo

Vascular function and structure is maintained or improved by long term administration of physiologically acceptable compounds which enhance the level of endogenous nitric oxide or other intermediates in the NO induced relaxation pathway in the host. Alternatively, or in combination, other compounds may be administered which provide for short term enhancement of nitric oxide, either directly or by physiological processes.

Enhancement of vascular function by modulation of endogenous nitric oxide production or activity

Growing community of inventors

Durham, NC, United States of America

Victor J Dzau