Loma Linda University

The United States Government As Represented by the Department of Veterans Affairs

Lau, Kin-hing, William

Baylink, David J

Qin, Xuezhong

Kin-Hing William Lau

David J Baylink

Subburaman Mohan

Xuezhong Qin

Susan L Hall

Shin-Tai Chen

Xiaobing Zhang

Xiao-Bing Zhang

Wanqiu Chen

A vector for generating induced pluripotent stem cells from human target cells comprising a) a vector backbone, b) exactly two, three or four transcription and reprogramming factor genes, each gene separated by a 2a self-cleavage peptide sequence, c) a spleen focus-forming virus promoter, and d) a post-transcriptional regulatory element Wpre, with or without an anti-apoptotic factor gene. A method for generating integration-free induced pluripotent stem cells, the method comprising: a) providing target cells, b) providing one or more than one vector according to the present invention, c) transducing or transfecting the target cells with the one or more than one vector, and d) culturing the transduced or transfected cells in a cell culture, thereby generating integration-free induced pluripotent stem cells.

Vectors and methods for the efficient generation of integration/transgene-free induced pluripotent stem cells from peripheral blood cells

Methods are disclosed herein for increasing bone mass and strength or bone fracture healing in a subject. The methods include administering to the subject a therapeutically effective amount of multipotent stem cells, wherein each multipotent stem cell is transformed with a recombinant nucleic acid molecule comprising a heterologous promoter operably linked to a nucleic acid encoding platelet derived growth factor (PDGF) B, and wherein the multipotent stem cells express a sufficient amount of PDGFB to increase bone mass and strength or bone fracture healing. A lentiviral vector also is disclosed that includes a phosphoglycerate kinase-1 (PGK) promoter operably linked to a nucleic acid encoding PDGFB.

Systemic and local ex vivo gene therapy of the skeleton

The present disclosure provides compositions and methods for increasing bone growth and/or enhancing wound healing, for example, fracture repair. The disclosure provides recombinant nucleic acids useful for promoting bone growth. For example, the disclosure provides recombinant nucleic acids that encode a fibroblast growth factor-2 (FGF-2) analog. The disclosure also provides vectors and cells incorporating these nucleic acids, as well as FGF-2 analogs encode by them. The disclosure also provides a mouse system of bone marrow transplantation and methods for producing as well as methods for using the system. Methods for inducing division and/or inducing differentiation of a hematopoietic stem cell are also provided, as are methods for enhancing bone growth and/or wound repair (for example, fracture repair).

Compositions and methods for osteogenic gene therapy

Gene-modified, inflammation-specific monocytes that comprise a 1-alpha-hydroxylase gene, where the 1-alpha-hydroxylase gene is expressed to produce functional 1-alpha-hydroxylase enzyme when the monocytes transdifferentiate into gene-modified, inflammation-specific macrophages. Gene-modified, inflammation-specific macrophages that comprise a 1-alpha-hydroxylase gene. A method for treating one or more than one inflammation-related condition or disease, the method comprising administering gene-modified, inflammation-specific monocytes that comprise a 1-alpha-hydroxylase gene, where the 1-alpha-hydroxylase gene is expressed to produce functional 1-alpha-hydroxylase enzyme when the monocytes transdifferentiate into gene-modified, inflammation-specific macrophages.

Agents and method for treating inflammation-related conditions and diseases

Composition and methods for osteogenic gene therapy

Growing community of inventors

Redlands, CA, United States of America

Kin-Hing William Lau