Cornell Research Foundation Inc.

Other

Baylor College of Medicine

The State University of New York

Cornell University

Mdx Medical, Inc.

Todd K Rosengart

Ronald G Crystal

Megumi Mathison

Raymond A Hartman

Vivek Singh

Vivekkumar B Patel

Hongran Wang

Erin Lynn Reineke

Austin J Cooney

Neil R Hackett

Mitchel Rothschild

Christine Parlamis

Xiaohuai Zhou

Robert Gersch

Charles A Mack, Iii

Vivek P Singh

Embodiments of the disclosure include methods and compositions for in situ cardiac cell regeneration, including transdifferentiation of cardiac cells to cardiomyocytes. In particular embodiments, in situ cardiac cell regeneration encompasses delivery of p63 shRNA and one or both of Hand2 and myocardin, and in specific embodiments further includes one or more of Gata4, Mef2c, and Tbx5. In specific aspects of the disclosure, adult cardiac fibroblasts are reprogrammed into cardiomyocytes using viral vectors that harbor p63 shRNA and one or both of the transcription factors Hand2 and myocardin.

p63 inactivation for the treatment of heart failure

Provided is a method of treating coronary artery disease in a mammal, comprising administering to a region of the heart of the mammal (a) a first vector encoding one or more angiogenic proteins which induce vascularization in the heart of the mammal, and (b) a second vector encoding one or more cardio-differentiating transcription factors which induce the production of induced cardiomyocytes (iCM) in the heart of the mammal, whereby the coronary artery disease in the mammal is treated. In a preferred embodiment, the first vector is an adenoviral vector encoding VEGF and the second vector is a lentiviral vector encoding Gata4, Mef2c, and Tbx5 (GMT).

Angiogenic conditioning to enhance cardiac cellular reprogramming of fibroblasts of the infarcted myocardium

A method of predicting a quality of a professional based on quality measures of the professional is provided. The method includes collecting recommendations associated with the professional and determining an independent variable for the professional based on the recommendations received for the professional. Here, the independent variable reflects the quality of the professional. The method also includes comparing the independent variable with quality measures associated with the professional and generating a model based on the comparison between the independent variable and the quality measures. The model associates each of the quality measures with the quality of the professional. Particularly, the model assigns a weight to each of the quality measures based on the probativeness of the quality measure in relation to the quality of the professional. Thus, the quality measure of the professional may be used to determine the overall quality of the professional.

Method for determining the quality of a professional

An apparatus for cutting and removing a tissue is described, which includes a rotational axle device, at least one non-mechanical cutting device radially disposed from the rotational axle device, at least one device capable of protecting the heart ventricle, and a first collapsible plate. Also described is a method for cutting a tissue, such as a heart valve using the apparatus of the present invention and temporary placing a device capable of protecting the heart ventricle until a percutaneous heart valve is placed.

Apparatus and method for cutting a heart valve

Graft delivery systems and methods for performing a cardiac by-pass procedure using a graft or a mammary artery are described. A combination of catheters and guide devices through the aorta, coronary artery, and the thoracic region can be used to accomplish these procedures.

Method and apparatus for performing an anastamosis

The present invention provides a method for enhancing the level of perfusion of blood to a target tissue, treating a target tissue suffering from or at risk of suffering from ischemic damage, inducing angiogenesis in a target tissue, and/or inducing collateral blood vessel formation in a target tissue affected by or at risk of being affected by a vascular occlusion. The present inventive method comprises administering to the target tissue a dose of a pharmaceutical composition comprising (a) a pharmaceutically acceptable carrier and (b) an adenoviral vector comprising a DNA encoding an angiogenic peptide, such that the level of perfusion of blood to the target tissue is enhanced, the dose has a therapeutic or prophylactic effect on the target tissue, angiogenesis is induced in the target tissue, and/or the adenoviral vector contacts a region including the source, the terminus, and an area therebetween for the collateral blood vessel formation, and collateral blood vessel formation is induced.

Multiple site delivery of adenoviral vector directly into muscle for the induction of angiogenesis

The invention provides a steerable device for the delivery of a therapeutic solution, in particular, an angiogenesis-promoting substance into a heart, and a method of delivering such a substance into the heart. The device includes an elongated needle which the physician may steer by asserting a tensioning force on a steering cable coupled to the needle toward its distal end. A axially-slidable steering sleeve is disposed about the needle and the steering cable, and the position of the steering sleeve may be adjusted to control the radius of flexure of the needle. The needle body is flexible enough to maneuver around thoracic and cardiac geometry, yet sufficiently rigid to facilitate such maneuvering. The needle may also have a stop, or platform, spaced from the distal needle tip to stabilize the needle in the cardiac tissue. According to a method of the invention, the needle may be inserted into the heart tissue through lung tissue adhering to the heart, as is common in re-operative patients. The platform may either transit the needle as the platform contacts the lung or heart tissue, or the platform may move forward to contact tissue as needle contact with heart tissue is confirmed.

Remote sensing gene therapy delivery device and method of administering a therapeutic solution to a heart

The present invention provides a method for enhancing the level of perfusion of blood to a target location in a host comprising establishing a gradient of an angiogenic mediator of increasing concentration from a source location (e.g., an angiogenically functional location) in the host to a target location (e.g., an angiogenically dysfunctional location) in the host, such that the level of perfusion of blood to the target location in the host is enhanced.

Method of inducing angiogenesis

The invention is directed to a device and method for delivering a therapeutic substance (,) to a bodily tissue in a minimally invasive manner. The device includes an elongate flexible tubular member (,) having a proximal end (,) and a distal end (,). A control lever (,) is provided for enabling the distal end (,) of the tubular member (,) to be controllably flexed in a transverse manner for positioning the distal end (,) of the tubular member (,) proximate to the bodily tissue to be treated. A hollow needle (,) is disposed at the distal end (,) of the tubular member (,) for delivering the therapeutic substance (,) into the bodily tissue. A marking device (,) is also included for indicating the location where an injection has been made in the tissue. This enables the surgeon to keep track of the areas in which injections are made so that the therapeutic substance (,) may be evenly distributed over a desired area of treatment. A method for using the device is also disclosed wherein a patient's lung (,) is partially collapsed to enable access to areas of the heart (,). The therapeutic substance (,) may be injected into the patient's myocardium (,) by passing the needle (,) directly through the patient's pericardium (,). The invention is particularly useful for treatment of ischemic heart disease by gene therapy.

Minimally invasive gene therapy delivery and method

The present invention provides a method of expressing an exogenous nucleic acid in a mammal. The method comprises non-systemically administering to a non-neuronal tissue of said mammal an exogenous nucleic acid operatively linked to a promoter. The exogenous nucleic acid is proximal to at least one native parvoviral inverted terminal repeat and does not require encapsidation. The expression of the exogenous nucleic acid in the tissue is not substantially diminished at 28 days after administration of the exogenous nucleic acid.

Method of expressing an exogenous nucleic acid

The invention is directed to a device and method for delivering a therapeutic substance to a bodily tissue in a minimally invasive manner. The device includes an elongate flexible tubular member having a proximal end and a distal end. A control means is provided for enabling the distal end of the tubular member to be controllably flexed in a transverse manner for positioning the distal end of the tubular member proximate to the bodily tissue to be treated. A hollow needle is disposed at the distal end of the tubular member for delivering the therapeutic substance into the bodily tissue. A marking means is also included for indicating when a injection has been made in the tissue. The invention is particularly useful for treatment of ischemic heart disease by gene therapy.

Minimally invasive gene therapy delivery device and method

The present invention on embodies a device and method for creating a bloodless field at an incision site in a blood vessel. The invention includes a perfusion tube for allowing perfusion of blood past the incision site. A pair of conical occlusive members are mounted on either end of the perfusion tube for preventing blood from flowing into the surgical site. A tubular stem depends from the tube, and includes a movable stopper which may be moved between a first position for blocking blood flow through the perfusion tube, and a second position for enabling blood to perfuse through the perfusion tube. With the movable stopper in the first position, a first end of the device may be inserted through a small incision into the upstream side of a blood vessel so that the blood flow is blocked. The second end of the device may then be inserted in the downstream side of the incision. The stopper may then be moved to the second position so that blood is free to flow through the perfusion tube. The downstream tissue will thus continue to receive a supply of oxygenated blood, while the portion of the blood vessel between the occlusive members remains blood-free.

Perfusion and occlusion device and method

A gene transfer delivery apparatus and method includes a plurality of syringes retained in a syringe-retaining portion. Each syringe contains a predetermined quantity of treatment solution. The treatment solution may be expelled through a needle on the end of each syringe by depressing the syringe plunger associated with each syringe. The syringe-retaining portion of the delivery device is connected to a plunger portion which contains a main plunger capable of depressing the syringe plungers simultaneously. Since the syringe plungers are depressed uniformly, the delivery device allows for the precise injection of a fixed volume of fluid at plural locations and at a predetermined depth. A spring-biased platen is mounted on the device for flattening the tissue prior insertion of the needles into the tissue. A method of using the delivery device for treatment of ischemic heart disease by gene therapy is also disclosed.

Growing community of inventors

Highland Park, IL, United States of America

Todd K Rosengart