Blacksburg, VA, United States
Blacksburg, VA, United States

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Patent
Revivicor Inc. | Date: 2017-03-08

The present invention provides ungulates, including pigs, expressing CTLA4-Ig, as well as tissue, organs, cells and cell lines derived from such animals. Such animals, tissues, organs and cells can be used in research and medical therapy, including xenotransplantation, and nucleic acid constructs and vectors useful therein.


Mohiuddin M.M.,U.S. National Institutes of Health | Singh A.K.,U.S. National Institutes of Health | Corcoran P.C.,U.S. National Institutes of Health | Hoyt R.F.,Science Research Laboratory Inc. | And 3 more authors.
Journal of Thoracic and Cardiovascular Surgery | Year: 2014

Objectives Cardiac transplantation and available mechanical alternatives are the only possible solutions for end-stage cardiac disease. Unfortunately, because of the limited supply of human organs, xenotransplantation may be the ideal method to overcome this shortage. We have recently seen significant prolongation of heterotopic cardiac xenograft survival from 3 to 12 months and beyond. Methods Hearts from genetically engineered piglets that were alpha 1-3 galactosidase transferase knockout and expressed the human complement regulatory gene, CD46 (groups A-C), and the human thrombomodulin gene (group D) were heterotropically transplanted in baboons treated with antithymocyte globulin, cobra venom factor, anti-CD20 antibody, and costimulation blockade (anti-CD154 antibody [clone 5C8]) in group A, anti-CD40 antibody (clone 3A8; 20 mg/kg) in group B, clone 2C10R4 (25 mg/kg) in group C, or clone 2C10R4 (50 mg/kg) in group D, along with conventional nonspecific immunosuppressive agents. Results Group A grafts (n = 8) survived for an average of 70 days, with the longest survival of 236 days. Some animals in this group (n = 3) developed microvascular thrombosis due to platelet activation and consumption, which resulted in spontaneous hemorrhage. The median survival time was 21 days in group B (n = 3), 80 days in group C (n = 6), and more than 200 days in group D (n = 5). Three grafts in group D are still contracting well, with the longest ongoing graft survival surpassing the 1-year mark. Conclusions Genetically engineered pig hearts (GTKOhTg.hCD46.hTBM) with modified targeted immunosuppression (anti-CD40 monoclonal antibody) achieved long-term cardiac xenograft survival. This potentially paves the way for clinical xenotransplantation if similar survival can be reproduced in an orthotopic transplantation model. © 2014 by The American Association for Thoracic Surgery.


Cooper D.K.C.,University of Pittsburgh | Ayares D.,Revivicor Inc.
International Journal of Surgery | Year: 2011

There is a limited availability of deceased human organs and cells for the purposes of clinical transplantation. Genetically-engineered pigs may provide an alternative source. Although several immune barriers need to be overcome, considerable progress has been made in experimental models in recent years, largely through the increasing availability of pigs with new genetic modifications.Pig heterotopic heart graft survival in nonhuman primates has extended for 8 months, with orthotopic grafts supporting life for almost 2 months. Life-supporting kidney transplants have functioned for almost 3 months. The current barriers are related to coagulation dysfunction between pig and primate that results in thrombotic microangiopathy and/or a consumptive coagulopathy, which may in part be related to molecular incompatibilities in the coagulation systems of pigs and primates. Current efforts are concentrated on genetically-modifying the organ- or islet-source pigs by the introduction of 'anticoagulant' or 'anti-thrombotic' genes to provide protection from the recipient coagulation cascade and platelet activation.Progress with pig islet xenotransplantation has been particularly encouraging with complete control of glycemia in diabetic monkeys extending in one case for >12 months. Other areas where experimental data suggest the possibility of early clinical trials are corneal xenotransplantation and pig neuronal cell xenotransplantation, for example, in patients with Parkinson's disease.With the speed of advances in genetic engineering increasing steadily, it is almost certain that the remaining problems will be overcome within the foreseeable future, and clinical allotransplantation will eventually become of historical interest only. © 2010.


The present invention provides ungulate animals, tissue and organs as well as cells and cell lines derived from such animals, tissue and organs, which lack expression of functional endogenous immunoglobulin loci. The present invention also provides ungulate animals, tissue and organs as well as cells and cell lines derived from such animals, tissue and organs, which express xenogenous, such as human, immunoglobulin loci. The present invention further provides ungulate, such as porcine genomic DNA sequence of porcine heavy and light chain immunogobulins. Such animals, tissues, organs and cells can be used in research and medical therapy. In addition, methods are provided to prepare such animals, organs, tissues, and cells.


The present invention provides tissues derived from animals, which lack any expression of functional alpha 1,3 galactosyltransferase (alpha-1,3-GT). Such tissues can be used in the field of xenotransplantation, such as orthopedic reconstruction and repair, skin repair and internal tissue repair or as medical devices.


Patent
Revivicor Inc. | Date: 2016-05-05

The present invention provides certain animals, and in particular porcine animals, tissue and cells derived from these, which lack any expression of functional alpha 1,3 galactosyltransferase (aGT) and express one or more additional transgenes which make them suitable donors for pancreatic islet xenotransplantation. Methods of treatment and prevention of diabetes using cells derived from such animals are also provided.


The present invention provides tissues derived from animals, which lack any expression of functional alpha 1,3 galactosyltransferase (alpha-1,3-GT). Such tissues can be used in the field of xenotransplantation, such as orthopedic reconstruction and repair, skin repair and internal tissue repair or as medical devices.


The invention provides cells and animals, as well as methods of producing cells and animals, that express at least one interfering RNA molecule to regulate the expression of a specific gene or family of genes. The invention further provides novel iRNA molecules, as well as DNA templates for producing iRNA molecules.


The present invention is a porcine animal, tissue, organ, cells and cell lines, which lack any expression of functional alpha 1,3 galactosyltransferase (alpha 1,3GT). These animals, tissues, organs and cells can be used in xenotransplantation and for other medical purposes.


Patent
Revivicor Inc. | Date: 2010-06-23

The production of genetically modified animals, in which the genetic modifications are engineered in somatic cells cultured in vitro by gene targeting, is described. Genetically modified cells may then be used as nuclear donors loci in animal chromosomes which are suitable sites for transgene addition to cells.

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