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Researchers Successfully Clone First Knockout Miniature Swine; Study Represents Important Step Towards Animal-To-Human Organ Transplantation

Date:
January 9, 2002
Source:
University Of Missouri-Columbia
Summary:
Researchers from the University of Missouri-Columbia and Immerge BioTherapeutics Inc. (a BioTransplant Incorporated/Novartis Pharma AG joint venture company) reported they have successfully cloned the world's first miniature swine with a specific gene "knocked out" of their DNA. This particular knockout moves scientists closer to making animal-to-human organ transplantation a reality, offering additional hope to the more than 75,000 Americans currently awaiting organs, 16 of whom die each day while waiting.

Columbia, MO, January 3, 2002 - Researchers from the University of Missouri-Columbia and Immerge BioTherapeutics Inc. (a BioTransplant Incorporated/Novartis Pharma AG joint venture company) reported they have successfully cloned the world's first miniature swine with a specific gene "knocked out" of their DNA. This particular knockout moves scientists closer to making animal-to-human organ transplantation a reality, offering additional hope to the more than 75,000 Americans currently awaiting organs, 16 of whom die each day while waiting. The study is reported online by the journal Science at the Science Express web site (http://www.sciencexpress.org).

"The greatest challenge in xenotransplantation - or the transplanting of a cell, tissue or organ from one species to another - is overcoming the body's massive immune response after it perceives a 'foreign' organ," said Randall Prather, Ph.D., MU Distinguished Professor of Reproductive Biotechnology. "This modification eliminates the gene that triggers this response, opening the door for further advances."

The aggressive (hyperacute) rejection response seen in previous research occurs when human antibodies attach to sugar molecules on the surface of the transplanted pig organ's cells. Once they attach, the antibodies kill the cells. In this particular line of miniature swine, however, the gene that produces this sugar molecule, called a-1,3-galactosyltransferase or GGTA1, has been eliminated. Without the sugar, the antibodies can't attach, and therefore the rejection process can't begin.

Today's report represents the first targeted modification of the pig genome and only the second in any large animal. It also is the first nuclear transfer-derived miniature swine. The choice of pig line is another unique feature of this study and represents advancement towards an important safety hurdle for xenotransplantation.

"We have been actively developing a line of miniature swine that offers many advantages as a potential donor for xenotransplantation, including their organ size, which is appropriate for human recipients," said Julia Greenstein, Ph.D., CEO and President, Immerge BioTherapeutics Inc., whose company knocked out the GATA1 gene. "Another advantage is that preliminary research shows that cells from this line of pigs, in contrast to most other cells tested, don't have the capacity to spread porcine endogenous retrovirus to human cells in culture."

Endogenous retroviruses are part of the natural genetic makeup of all mammals and are not believed to cause any illness to the species that they inhabit. Although the risk of any harm posed by PERV to xenotransplant recipients may be purely theoretical, use of this line f miniature swine would help minimize this particular risk of this new technology.

"Based on the success reported today, we can now proceed with a pig strain chosen solely for their advantages in xenotransplantation rather than their large-scale availability," said Robert Hawley, Ph.D., Associate Director of Animal Genetic Engineering, Immerge BioTherapeutics Inc. "We believe this line of miniature swine offers the greatest potential for clinical use in humans, and we're working closely with the University of Missouri-Columbia and our commercial partner, Infigen Inc., to develop these swine with this goal in mind."

The University of Missouri-Columbia has a long standing research collaboration with Immerge BioTherapeutics and BioTransplant Incorporated in the field of porcine genetic engineering. The current collaboration is supported by a National Institutes of Health Small Business Innovative Research grant.

Immerge BioTherapeutics was formed on September 26, 2000, as a joint venture between Novartis Pharma AG and BioTransplant Incorporated. The company, which began operations on January 2, 2001, focuses its research efforts toward developing therapeutic applications for xenotransplantation. The name of the company derives from its use of immunology to address the challenges of conducting transplants between species.


Story Source:

The above story is based on materials provided by University Of Missouri-Columbia. Note: Materials may be edited for content and length.


Cite This Page:

University Of Missouri-Columbia. "Researchers Successfully Clone First Knockout Miniature Swine; Study Represents Important Step Towards Animal-To-Human Organ Transplantation." ScienceDaily. ScienceDaily, 9 January 2002. <www.sciencedaily.com/releases/2002/01/020109080035.htm>.
University Of Missouri-Columbia. (2002, January 9). Researchers Successfully Clone First Knockout Miniature Swine; Study Represents Important Step Towards Animal-To-Human Organ Transplantation. ScienceDaily. Retrieved September 2, 2014 from www.sciencedaily.com/releases/2002/01/020109080035.htm
University Of Missouri-Columbia. "Researchers Successfully Clone First Knockout Miniature Swine; Study Represents Important Step Towards Animal-To-Human Organ Transplantation." ScienceDaily. www.sciencedaily.com/releases/2002/01/020109080035.htm (accessed September 2, 2014).

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