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Xenotransplantation Technology The goal is to produce genetically modified animals (pigs) to provide human compatible cells (i.e., islets) and organs and tissues for use in transplant surgery (xenografts). In order for xenografts to succeed for any application, it will be imperative to stop the first line of immune response to cross-species transplantation, what is termed Hyperacute Rejection ("HAR"). This is the primary focus of Revivicor in the near term, and successfully averting HAR is seen by most experts in the field as the critical milestone to achieve initial graft acceptance. HAR may be averted by removing the major xeno-antigen (1,3 a-gal) from pig cells through genetic modification (targeted gene knockout and nuclear transfer), or by inhibiting the activation of the complement cascade. Revivicor is addressing both using strategies that are novel and proprietary. Click here for more xenotransplantation background information. |
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introduced above, PPL announced in March 2000 that it was the world’s first company
to successfully clone piglets, and in April 2001, PPL announced that it had cloned
transgenic piglets from genetically modified pig cells, both of which were important steps
in the production of human compatible xenografts. In January, PPL announced that cloned
piglets were born which have been confirmed to have their 1,3 a -gal gene deleted
("knock out"). These so-called "knock out" pigs are thus genetically
engineered to deactivate the gene which causes the human immune system to reject pig
organs, tissues, and cells, and in this case, only one of the two allelles required for
knockout had been completed. PPL followed up with its announcement in August 2002, that
"double knockout" piglets had been born, meaning both alleles of the a -gal gene
had been inactivated. The birth of these a-gal double knockout piglets marks the
achievement of the "holy grail" of the xenograft field, and provides the
critical breakthrough necessary for the near term application of xenografts. The xenograft
program was supported by a grant from the U.S. Department of Commerce Advanced Technology
Program ("ATP"), which totaled $2.0 million over three years. Tolerance As noted above, one of the problems of transplantation is that due to histo-incompatibility of donor/recipient tissues, large amounts of immune suppression drugs are needed to minimize the destructive power of the human immune response to foreign tissue. Many groups involved in the field of regenerative medicine however seem to be neglecting this issue, focusing only on obtaining the stem cells and/or derivation of specific cell tissue types. While there are many groups who have been successful in deriving human stem cells or are creating genetically modified pigs for xenografts, there will still be a need to modulate the immune system response. Revivicor understands these issues, and has developed separate and proprietary technologies to address these issues. Revivicor’s technology provides tolerization of the recipient’s immune system at the cellular level, building in protection by genetically engineering the cells even without a genetic match available. In the case of xenografts, Revivicor has proprietary technology which works to minimize the long-term T Cell mediated destruction of the graft through pre-exposure of the recipient to specially-designed porcine cells prior to surgery and the introduction of the graft. Tolerogenic cells, which are derived by differentiation of embryonic or adult stem cells, are a major focus of the stem cell program, and have applications for both cellular and whole organ transplants. |
