Geron Corporation

Roslin Institute (edinburgh)

J Michael Schiff

Joseph D Gold

A John Clark

Chris Denning

Jim McWhir

This disclosure provides a system for generating animal tissue with carbohydrate antigens that are compatible for transplantation into human patients. The tissue is inactivated homozygously for expression of &#x3b1;(1,3)galactosyltransferase, and comprises a transgene for &#x3b1;(1,2)fucosyltransferase. As a result, cell-surface N-acetyl lactosamine is not converted to the Gal&#x3b1;(1,3)Gal xenoantigen. Instead, it is converted to Fuc&#x3b1;(1,2)Gal, which is H substance, a self-antigen in humans. The tissue may also contain A or B-transferase, which will cause H substance to be converted into other ABO blood group antigens for compatibility with patients of the same blood type. This invention improves transplant compatibility of the xenograft tissue by lessening the risk of reactions resulting from xenoantigen and unconverted N-acetyl lactosamine acceptor determinants.

Animal tissue with carbohydrate antigens compatible for human transplantation

This invention provides a system for producing differentiated cells from a stem cell population for use wherever a relatively homogenous cell population is desirable. The cells contain an effector gene under control of a transcriptional control element (such as the TERT promoter) that causes the gene to be expressed in relatively undifferentiated cells in the population. Expression of the effector gene results in expression of a cell-surface antigen that can be used to deplete the undifferentiated cells. Model effector sequences encode glycosyl transferases that synthesize carbohydrate xenoantigen or alloantigen, which can be used for immunoseparation or as a target for complement-mediated lysis. The differentiated cell populations produced are suitable for use in tissue regeneration and non-therapeutic applications such as drug screening.

Selective antibody targeting of undifferentiated stem cells

This disclosure provides a system for specifically killing cancer cells which can be used in the course of human therapy. Vectors of the invention comprise an encoding sequence for a glycosyltransferase, under control of a tumor or tissue specific transcriptional control element, such as the promoter for telomerase reverse transcriptase. Exemplary glycosyltransferases are the A or B transferase enzymes, which cause the cancer cells to express ABO histo blood group allotypes against which humans have naturally occurring antibody. This provides for ongoing surveillance for newly emerging cells with a malignant phenotype.

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Menlo Park, CA, United States of America

J Michael Schiff