At the most recent conference at the National Academy of Sciences, Dr. George Church of Harvard Medical School presented his use of the new gene-editing method known as CRISPR to alter many individual genes in pig embryos. These genes’ elimination, in an unprecedented number through Crispr technology, has the potential to make pig-to-human organ transplants much safer and more viable in the future.
When it comes to human organ transplants, there is a chronic undersupply. According to the American Transplant Foundation, “On average, 21 people die every day from the lack of available organs for transplant.” This amounts to about seven percent of the people on the waitlist dying before receiving a transplant.
While it seems strange to replace human organs with pigs’, it is decidedly less macabre than waiting for another person to die so that their organs can be taken. Beyond the ethical issues involved in harvesting animal organs for people, an issue with this practice, broadly known as xenotransplantation, is that, while pigs and humans do share similar internal physiologies on the macroscale, the genetic and physical differences are vast.
One such difference that makes this practice especially risky is the existence of Porcine Endogenous Retroviruses, or PERVs. These are viral genes that have been hardcoded into a pig’s genome from exposure to viruses, and which can produce these viruses throughout the life cycle of the cell. In cell culture, the viruses encoded by these PERVs have been able to infect human cells.
Which is why Dr. Church and his team set out to remove these PERVs from pig embryo cells. Previous attempts to replace or eliminate these 62 sequences using other methods have either failed or produced cells that died soon after. By harnessing the power or Crispr, Dr. Church has been able to not only alter all 62 of these PERV genes, but the altered cells have remained viable.
Crispr utilizes a built-in immune response in bacteria to edit the genes of any number of other organisms. In bacteria, there are no white blood cells or other immune cells to fend off viruses. Instead, they rely on the Crispr system. Upon infection by a virus, the cell will steal a bit of the virus’s DNA and add it to its own, filing this unique genetic imprint away so that, if the bacterium encounters this virus again, it will recognize it and degrade the invading virus’s DNA.
In the past few years, scientists have managed to harness this specific genetic recognition and subsequent DNA alteration to edit genetic material across a wide range of species. Not only has Crispr proven to be accurate at changing genes, but it is also quicker and much cheaper than other methods that can demand prohibitive sums of money and time.
Nevertheless, this method had only been used to change genes a few at a time. The 62 PERV genes that Dr. Church and his lab inactivated represent a new step forward in the use of Crispr to modify multiple genes.
Dr. Church and his colleagues were aided by the fact that the PERV genes in the pig genome were very similar, and so it was not necessary to engineer 62 different genes to recognize each individual PERV. These engineered genes were then inserted into the pig cells’ DNA to encode proteins that would root out the PERVs and disable the viral genes.
These pig cells, while free of the viruses that can cause harm to human transplant recipients, are still not ready for the spotlight. Dr. Church is currently using Crispr to neutralize another aspect of the xenotransplantation problem: tissue rejection.
When the human body comes into contact with foreign tissue (such as germs or a transplant), the immune response is activated. Individual cells have proteins on their surfaces that indicate what type of cell it is (these are the proteins that determine blood type), and so when a pig cell is introduced to a human body, our bodies recognize away that it doesn’t belong.
Dr. Church and his lab are working to alter the 25 or so genes that give rise to these individual markers so that, upon exposure to a transplant recipient’s immune system, the alarm won’t sound and the transplant will be accepted. While he will be using Crispr, it will not necessarily be as straightforward as inactivating the PERVs, since these genes are not as similar to one another as the PERVs were.
Crispr has only been a household name in the scientific world for a few years, but its use as a gene-editing method is quickly becoming more prevalent. There is no indication of how useful or far-reaching Crispr can be for treating disease, but scientists are looking into a range of other possible uses, such as targeting antibiotic-resistant bacteria and gene therapy.
While rejection-resistant, PERV-less xenotransplants are still a few years away, Dr. Church’s research and the expansion of Crispr gene editing technology signal an optimistic development in unlocking the mysteries of DNA for the advancement of human health.
Photos courtesy of google.
