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Genetic engineering in the pig. Gene knockout and alternative techniques
B Vanhove1, J P Renard, J P Soulillou
1Institut National de la Santé et de la Recherche Médicale (INSERM), Unit 437, CHU-Hotel Dieu, Nantes, France. bvanhove@nantes.inserm.fr
Annals of the New York Academy of Sciences
|February 3, 1999
Summary
Genetic engineering of xenotransplant donor endothelial cells (EC) targets hyperacute rejection. Strategies include modifying alpha 1,3Gal antigen and complement regulatory proteins for improved graft survival.
Area of Science:
- Immunology
- Transplantation Biology
- Genetic Engineering
Background:
- Endothelial cells (EC) are key targets in hyperacute and delayed graft rejection.
- Genetic modification of donor EC is crucial for xenotransplantation success.
Purpose of the Study:
- To review strategies for genetically modifying xenotransplant donor endothelial cells.
- To explore methods for overcoming challenges in xenotransplantation, particularly in pigs.
Main Methods:
- Review of genetic engineering techniques targeting endothelial cells.
- Analysis of antigen knockout (alpha 1,3Gal) and complement regulatory protein transgenesis.
- Discussion of alternative methods for genetic modification in species lacking ES cells.
Main Results:
- Alpha 1,3Gal antigen knockout reduces xenoantibody targets and innate cellular response.
- Transgenesis of complement regulatory proteins is effective in preventing complement-mediated damage.
- In vitro studies suggest targeting apoptosis, thrombotic microenvironment, and T-cell costimulatory proteins (CD40, B7) are viable strategies.
Conclusions:
- Genetic modification of donor endothelial cells is essential for successful xenotransplantation.
- Targeting specific antigens and regulatory proteins can mitigate immune rejection.
- Alternative genetic engineering approaches are needed for species like pigs lacking established ES cell lines.