By Matthew Willett
Infigen Inc. plans to win the race to clone transgenic knockout pigs without the genetic barriers to xenotransplantation ¿ cross-species organ transfer ¿ through a deal to produce less porcine porkers with more human organs.
Deforest, Wis.-based Infigen entered a partnership with Immerge BioTherapeutics Inc., a joint venture between Novartis Pharma AG, of Basel, Switzerland, and BioTransplant Inc., of Cambridge, Mass., to use nuclear transfer (NT) technology to develop the swine.
Privately held Infigen will provide Immerge with exclusive access to its porcine NT technology. Infigen¿s program already has cloned both unaltered and transgenic pig litters.
Immerge will provide the vectors for specific genes and cells from miniature swine, and Infigen will clone knockout swine that lack both the genetic imperative to produce a porcine organ surface compound that triggers human rejection, the a-1,3-galactosyl transferase gene, and infection by PERV, or porcine endogenous retrovirus, which has the potential to infect humans.
The knockout pigs could be the last step in a long process. Infigen reported in February its success at producing transgenic swine, pigs with altered genetic structures. Through a collaboration with Novartis the company has produced more than 30 pig clones.
Michael Bishop, Infigen¿s president and chief scientific officer, said the process is nearing the point when porcine organs could be transplant-ready. Miniature swine that lack PERV infection and whose organs are similar in size to human organs will be used.
¿We¿ve gone through the process with our Novartis arrangement to develop a repeatable cloning process in pigs,¿ Bishop said. ¿Then we¿ve demonstrated that we can, in fact, genetically modify pigs by introducing a gene into a cell and cloning those cells into pigs.
¿Now we have the specific gene for a-1,3-galactosyl transferase, and we¿re working with the joint venture between Novartis and BioTransplant, Immerge, and we¿re specifically making pigs through cloning using our cloning technology, cell culturing and genetic modification technology,¿ he said. ¿We¿re knocking out that part of the gene that¿s active and expressed in the pigs.¿
When the knockout pigs are produced, he added, further testing will determine whether additional genes need to be knocked out, but only after tests have confirmed that the knockout technique has worked.
Then testing in animals can begin.
¿There may be other additional genetic modification we want to make and test, and we¿ll determine that by trials and also work on that will be done by Immerge,¿ Bishop told BioWorld Today. ¿But then, after that we¿ll be looking at initial tests and transferring organs to such species as baboon, and we might, if the outcome is good, shorten the time frame to produce pigs for clinical testing in humans.¿
Financially, the agreement calls for Immerge to pay licensing fees to Infigen for the NT technology as well as milestone payments and three years of research funding.
The venture, too, is co-funded by an Advanced Technology Program Award from the Department of Commerce National Institute for Science and Technology. That grant was awarded in the 2000 competition.
The need for organs, and, therefore, the market for transplantable porcine organs, is vast. In the U.S. alone, more than 75,000 people are waiting for organs for transplant. Fifteen of them, the companies said, will die each day.