The Brigham and Women's Hospital, Inc.

Other

Leland Stanford Junior University

Corgentech, Inc.

Michael J Mann

Victor J Dzau

Gary H Gibbons

Richard E Pratt

Frank P Diet

Daniel P Griese

Afshin Ehsan

Paul Cherkas

James Julian Hazen

Giorgio Dell'Acqua

Lawrence H Cohn

Umer Sayeed-Shah

Heiko Von Der Leyen

A remediation system comprises a primary scalping screen, a primary pump and sump, a large diameter maximum density separator with flocculant injection ring, a secondary pump and sump, a small diameter maximum density separator with flocculant injection ring, a static sieve screen, a flocculation sump, a vibrating screen, a dewatering device, a tertiary sump and pump, a secondary flocculation tank, and a pugmill. Screens move water and particulates through the components. In this manner larger particles are separated from smaller particles and the particles are further dewatered.

Remediation system

In general, the invention features methods for delivering a composition to the liver in a non-surgical, percutaneous approach by utilizing the portal vein. Also disclosed are methods allowing for the liver-specific delivery of a composition.

Delivery of a composition to the liver by utilizing the portal vein

A method for implanting cells onto a prosthesis includes the steps of: (a) providing a prosthesis including a porous tube, where at least 25% of the pores on the inner surface of the tube have diameters of more than about 40 &mgr;m, at least 25% of the pores on the outer surface of the tube have diameters of less than about 30 &mgr;m, and the tube includes a substantially continuous layer of a biocompatible material; (b) contacting the prosthesis with a suspension of cells; and (c) providing a pressure differential between the inner surface and the outer surface, whereby the cells are retained in the pores of the inner surface. A method for obtaining an endothelial cell culture from a blood sample involved:(a) obtaining a sample for mononuclear cells from a blood sample; and (b) culturing the sample of mononuclear cells, without further cell separation, on a cell adhesive polymer-coated solid support in the presence of endothelial growth factors.

Methods for implanting cells

The invention provides a method and an apparatus for treating a tissue, such as a blood vessel, with therapeutic liquids, such as solutions of genes encoding therapeutic proteins.

Method and apparatus for tissue treatment

Disclosed herein is a method for implanting cells onto a prosthesis, including the steps of: (a) providing a prosthesis including a porous tube, where at least 25% of the pores on the inner surface of the tube have diameters of more than about 40 &mgr;m, at least 25% of the pores on the outer surface of the tube have diameters of less than about 30 &mgr;m, and the tube includes a substantially continuous layer of a biocompatible material; (b) contacting the prosthesis with a suspension of cells; and (c) providing a pressure differential between the inner surface and the outer surface, whereby the cells are retained in the pores of the inner surface. Also disclosed herein are methods for culturing cells for implantation.

The present invention is directed to an isoform of the p53 tumor suppressor and to polynucleotides that encode this isoform. The isoform may be used as a marker to indicate that cardiac cells have experienced hypoxia, as would occur during a myocardial infarction. In addition, vectors encoding the isoform may be transfected into cells as a means of regulating proliferation.

Compositions and methods based upon an isoform of p53

A method of enhancing injury-induced revascularization of a tissue as treatment of a disease, such as coronary artery disease, is described. The method involves (i) creating injury in a tissue (e.g., muscle, such as cardiac muscle) by, for example, use of a laser, an ultrasonic device, or a Thermal probe, and (ii) injecting into the tissue a revascularization-promoting molecule or a nucleic acid molecule encoding a revascularization-promoting molecules Also described is an apparatus that can be used to practice this method.

Method and apparatus for combining injury-mediated therapy and drug delivery

In general, the invention features methods for delivering a composition to the lung in a non-surgical, percutaneous approach by utilizing the pulmonary vasculature (i.e., the pulmonary arteries and veins). Also disclosed are methods allowing for the lung-specific delivery of a composition, as well as a catheter that includes a deployable arm.

Delivery of a composition to the lung

Naked nucleic acids (DNA, RNA, and/or analogs), drugs, and/or other molecules in an extracellular environment enter cells in living intact tissue upon application of pressure to the cells and extracellular environment. Nucleic acids localize to the cell nuclei. Transfection efficiencies greater than 90% are achievable for naked DNA and RNA. A sealed enclosure, defined by an enclosing means and/or tissue, contains the cells and their extracellular environment. The enclosure is pressurized to an incubation pressure on the order of atmospheres. A protective inelastic sheath may be used to prevent distension and trauma in tissue that is part of the enclosure boundary. Suitable enclosures include pressurization chambers and organs such as blood vessels or the heart. Parts of organs, entire organs, and/or entire organisms are pressurized. Suitable target tissue types include blood vessel (in particular vein) tissue, heart, kidney, liver, and bone marrow tissue. Gene therapy applications include ex-vivo treatment of grafts prior to transplantation, and in-vivo treatment of tissue. Useful therapy targets include cell cycle regulatory genes for blocking cell proliferation, and interleukin (IL) and cell adhesion molecule (CAM) genes for reducing immune responses to grafts.

Intracellular delivery of nucleic acids using pressure

The invention presents a system for inducing cells in living intact tissue, in vivo or ex vivo, to accept nucleotides from their extracellular environment and to localize those nucleotides into the cells' nuclei. This system relies on the fact that, when subjected to high pressure, cells take in nucleotides and localize those nucleotides into their nuclei with a transfection rate of greater than 90% in some cases. This invention employs various techniques for placing under high pressure either cells in isolated tissue cultures, or cells in tissues still connected to a living body. Such pressurization techniques include enclosing the tissue in an impermeable and inelastic sheath and injecting fluid into the tissue until a sufficiently high pressure is reached; placing a tissue culture in a dish and placing the dish in a pressurized chamber; mechanical pressurization techniques such as compression of a space containing fluids; occluding the ingress and egress of a vessel or organ to create a watertight compartment within the vessel or organ; and pressurization of an entire organism after delivery of nucleotide to the extracellular environment. This invention also employs various techniques for delivering a solution or suspension containing the nucleotide into the tissue; such techniques include the use of a syringe-like mechanism and a catheter.

Growing community of inventors

Newton, MA, United States of America

Michael J Mann