The following summarises the scientific approach at NZeno:
- Pig organs.
For many reasons, pig organs are the most suitable animal organs for humans. Pig kidneys are similar in size and structure to that of humans. Following transplantation in non-human primates, pig organs maintain normal fluid balance when the immune response against the pig kidneys are controlled by anti-rejection drugs.
- Safety of pig organs for humans.
The use of animal tissue to treat human disease is known as xenotransplantation. International regulatory guidelines require pigs used as a source of tissue for the treatment of humans to be free of infections that may be transmitted to humans. In New Zealand, pigs bred in a closed environment have been approved as a source of cells for human transplantation.
- Overcoming the rejection of pig organs.
Organs from other humans and from animals are rejected by the immune system when transplanted into a human recipient. Cells of the immune defence system and the antibodies they produce attack foreign tissues. In human to human organ transplant, the tissues are ‘cross-matched’ to minimise natural differences between donor and recipient tissues. Immune rejection is prevented with the use of immune suppressive drugs. Research in xenotransplantation has developed pigs whose tissues are missing selected genes that are the major cause of immune rejection.
- Gene editing technology.
In 2013, a gene editing technology known as the CRISPR/Cas9 system, was developed as a reliable way of inactivating genes. The pig genes responsible for immune rejection do not exist in humans and are not critical to life. NZeno intends to establish pig embryos that lack those pig genes and implant them into sows that are bred in an infection free environment. Pigs derived from such embryos will be selected following confirmation that the unwanted genes have been ‘knocked-out’.
- Pigs with genes knocked-out.
It is possible to obtain some confidence that the selected gene edited pig kidney would not be rejected by the human immune system. The standard cross-matching and screening tests used in human to human organ transplantation can be modified for pig to human transplantation. Prior to human transplantation, suitable gene edited pig kidneys would be selected from those pigs whose cells are not damaged when exposed to human immune cells. Recent research has shown that cells from gene knock-out pigs are poorly recognized by human antibodies against pig tissue.