University of Massachusetts

Kyowa Hakko Kirin Co., Limited

Kirin Holdings Kabushiki Kaisha

Kirin Beer Kabushiki Kaisha

Advanced Cell Technology, Inc.

W. R. Grace Co.-conn.

Aurox, LLC

Hematech, LLC

James M Robl

Yoshimi Kuroiwa

Jose Cibelli

Isao Ishida

Kazuma Tomizuka

Steven L Stice

Paul J Golueke

Barbara A Osborne

Richard A Goldsby

D Joseph Jerry

Poothappillai Kasinathan

Philippe Collas

F Abel Ponce De Leon

Amy Burnside

Eddie Sullivan

Stacy E Ferguson

Neal L First

Poothappillai K Kasinathan

Xiu Ying Gao

Frank Barnes

Randall S Prather

Vincent F Simmon

Bjorn Steen Skalhegg

Pedro Moreira

Catherine Blackwell

Kasinathan P

P Kasinathan

Methods for obtaining pluripotent (embryonic stem) cells from parthenogenetic embryos, especially primates, are provided. These cells are useful for producing differentiated cells, tissues and organs, especially human and non-human primate cells, tissues and organs.

Gynogenetic or androgenetic production of pluripotent cells and cell lines, and use thereof to produce differentiated cells and tissues

Methods for propagating haploid genomes of male or female origina and genetic screening and modification thereof are provided. These haploid genomes may be used to produce haploid embryos, and embryonic stem-like cells and differentiated cells. Also, these haploid genomes and cells containing, may be used as nuclear transfer donors to produce diploid nuclear transfer units. These diploid NT units e.g., human NT units, may be used to obtain pluripotent cells and differentiated cells and tissues.

Use of haploid genomes for genetic diagnosis, modification and multiplication

In general, the invention features genetically modified non-human mammals (e.g., bovines and other ungulates), and methods of making these mammals. In particular, the invention features transgenic ungulates having reduced levels of endogenous IgM heavy chain and/or prion protein.

Method of producing xenogenous antibodies using a bovine

The present invention relates to a method of producing an ungulate having both copies of the IgM heavy chain (mu) rag-1 and/or rag-2 gene eliminated from its genome. Animals which have IgM, rag-1 and/or rag-2 eliminated from their genome are unable to conduct the gene rearrangements that are necessary to generate the antigen receptors of B- or T-lymphocytes, and therefore will not develop native B- or T-cells. Because they are unable to produce B- and T-lymphocytes, these IgM, rag-1, or rag-2 ungulates cannot reject human hematopoietic stem cell preparations, and B- and T-lymphocytes which develop therefrom. Therefore, the present invention also involves injecting into IgM, rag-1, and/or rag-2 deficient ungulates, in utero or shortly after birth, human B- and T-lymphocytes whose immune systems produce human immunoglobulin that can be processed for therapeutic uses in humans.

Production of ungulates, preferably bovines that produce human immunoglobulins

The invention provides cloned transgenic ungulates (e.g., bovines) in which prion protein activity is reduced by one or more genetically engineered mutations. Desirably, these transgenic bovines are also genetically modified to express xenogenous (e.g., human) antibodies. Because of their resistance to prion-related diseases such as bovine spongiform encephalopy (also known as mad cow disease), these bovines are a safer source of human antibodies for pharmaceutical uses and a safer source of agricultural products.

Transgenic bovine having reduced prion protein activity and uses thereof

The invention features novel methods for the production of large quantities of xenogenous antibodies, such as human antibodies. Preferably, this result is effected by inactivation of IgM heavy chain expression and, optionally, by inactivation of Ig light chain expression, and by the further introduction of an artificial chromosome which results in the expression of xenogenous antibodies (e.g., non-bovine antibodies), preferably human antibodies.

Transgenic ungulates capable of human antibody production

The invention provides methods for altering the expression profile of a cell to convert the cell from one cell type to a desired cell type. These reprogrammed cells may be used in a variety of medical applications for treating a mammal in need of a particular cell type.

Methods for altering cell fate

The present invention relates to the production of a transgenic bovine which comprises a genetic modification that results in inactivation and loss of expression of its endogenous antibodies, and the expression of xenogenous antibodies, preferably human antibodies. This is effected by inactivation of the IgM heavy chain expression and, optionally, by inactivation of the Ig light chain expression, and by the further introduction of an artificial chromosome which results in the expression of non-bovine antibodies, preferably human antibodies.

Expression of xenogenous (human) immunoglobulins in cloned, transgenic ungulates

The invention provides methods for altering the expression profile of a cell to convert the cell from one cell type to a desired cell type (e.g., T-cells). These reprogrammed cells may be used in a variety of medical applications for treating a mammal in need of a particular cell type.

Methods for altering cell fate to generate T-cells specific for an antigen of interest

Transgenic bovines having reduced prion protein production

Transgenic animals and uses thereof

Transgenic bovines capable of human antibody production

An improved method of nuclear transfer involving the transplantation of donor differentiated pig cell nuclei into enucleated pig oocytes is provided. The resultant nuclear transfer units are useful for multiplication of genotypes and transgenic genotypes by the production of fetuses and offspring. Production of genetically engineered or transgenic pig embryos, fetuses and offspring is facilitated by the present method since the differentiated cell source of the donor nuclei can be genetically modified and clonally propagated.

Cloning pigs using non-quiescent differentiated donor cells or nuclei

Growing community of inventors

Brandon, SD, United States of America

James M Robl