Cedars-sinai Medical Center

Behrooz G Sharifi

Prediman Krishan Shah

Lai Wang

Embodiments of the present invention describe a method of changing the phenotype of monocytes and macrophages from a proinflammatory M1 phenotype to an anti-inflammatory M2 phenotype. The method can comprises providing a composition comprising a recombinant adeno-associated virus (rAAV) vector comprising an exogenous gene encoding ApoA-I Milano or a fragment thereof, and administering the composition to a mammal in need thereof to change the phenotype of monocytes or macrophages from a proinflammatory M1 phenotype to an anti-inflammatory M2 phenotype. By changing the phenotype of monocytes or macrophages from a proinflammatory M1 phenotype to an anti-inflammatory M2 phenotype, atherosclerosis can be treated. The present invention also describes a method of monitoring macrophage phenotypic switching and a method of assessing the efficacy of the treatment of atherosclerosis.

Atherosclerosis inhibition via modulation of monocyte-macrophage phenotype using Apo A-I Milano gene transfer

The invention relates to the discovery that mutations of serine residues of an AAV capsid results in significantly greater transfection efficiency than the wild type AAV2 virus. In one embodiment, the present invention provides a method of improving efficiency of gene transfer and/or gene therapy to a cell by inhibiting phosphorylation of one or more serine residues of a virus capsid protein, where the inhibition of the phosphorylation of one or more serine residues results in a decrease of ubiquitination of the virus capsid protein in the cell. In another embodiment, one of the one or more serine residues is Serine 264. In another embodiment, the Serine 264 residue is mutated to Alanine (S 264 A).

Effective vector platform for gene transfer and gene therapy

The invention relates to the isolation and use of hematopoietic and embryonic stem cells. Additionally, the inventors identified the peritoneal cavity as a new source of hematopoietic stem cells. In one embodiment, the invention provides methods of isolating progenitor and/or stem cells from the peritoneal cavity. In another embodiment, the invention provides methods of transporting progenitor and/or stem cells from the peritoneal cavity to another organ. In another embodiment, the present invention provides methods of regenerating bioengineered tissues and/or reconstituting an hematopoietic system.

Methods for isolating and using hematopoietic and embryonic stem cells of the peritoneal cavity

Peptides capable of interacting with smooth muscle cells are provided. Peptides are derived from Tenascin-C protein, particularly from the Fbg-L domain of Tenascin-C protein. Peptides of the present invention are useful in inhibiting smooth muscle cell migration. Methods of inhibiting smooth muscle cell adhesion and migration are also provided. Methods of the present invention may be used for treating intimal hyperplasia, restenosis, and atherosclerosis.

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Woodland Hills, CA, United States of America

Behrooz G Sharifi