31 Oct

Everything is good in the pig, especially for organ transplantation in humans. Unlike the saying goes, I would say that the pig would be our best friend (sorry Rex). It’s been several decades that the animal is used in medicine for the production of heparin (anticoagulant) and cardiac surgery (aortic valve). But very recently (October 5, 2015), at a conference on human genetics in Washington, George Church, a geneticist at Harvard Medical School and his colleagues announced that it would have produced an organ donor non-humain: the pig. This is the perfect candidate for the genetic closeness he shared with us. Indeed, its genome and ours are identical to 98%!

Strong genetic identity and so little resemblance ?

Before getting into the thick of it, I wish to raise one of your possible questions: How is it that man and the pig share 98% of genetic identity when we do not like him at all! Billy very good question! First, know that we are relatively similar to the pigs point of view of physiological and behavioral, whether you like it or not. Second, when we talk about “98% identity,” the remaining 2% correspond to approximately 60 million base pairs of different considering a genome at ~ 3 giga base pairs such as Man and pig (see DNA and cloning Billythekid). These have respectively 41 000 and 35 000 genes. If part of the 60 million differences are located at important genes, the phenotypic impact can be huge! This phenotype, that is to say, the set of observable characteristics in an organism is the result of all proteins encoded by the genome. However, the same gene can encode several different proteins in part due to alternative splicing phenomenon. In summary we are 2% have a tail corkscrew!

The two current major barriers to xenografts Pork / Human

Pork is the main species retained in the experimental xenotransplantation programs. But major challenges remain such as: immunological rejection and the risk of pathogen transmission.
If a transplanted pig organ in a primate (and we guess it would be the same in humans), rejection is instantaneous. George Church and his team probably overcome this immune rejection problem by modifying more than 20 pig embryos genes. These genes encode proteins which react our immune system. Many of these proteins are localized to the surface of pig cells. The list of these genes has not yet been published, but this would delay! The other risk is the pathogen transmission between pigs and humans. There are infectious agents called “endogenous” (as an integral part of the genome of the pig) which we can not get rid so easily. Porcine endogenous retroviruses (PERV) are components of the pig genome. As such they are present in all pig farms, regardless of their health levels. Some PERV naturally produced by porcine cells, infect human cells in vitro which raises questions about their possible transmission to humans in xenotransplantation context. However PERV can simply be genetically inactivated in the same way as the previous ~ 20 genes, ie enzymes that are biotechnology products CRISPR / cas9.

The principle endonucleases CRISPR / cas9

Sans titre

Figure 1 Editors-in-Chief Franco J. DeMayo and Thomas Spencer, biology of Reproduction

The endonucleases are enzymes that cleave DNA by hydrolysis. Some, such as “restriction endonucleases” intersect at specific positions of the DNA because they recognize a combination of 4 or 6 nucleotides (A, T, C and G). The probability in a human or pig genome of hitting the combination recognized by an endonuclease is high. It is thus not possible to use restriction endonucleases to modify a gene in a genome precisely without risking altering of other genes by cutting. For cons, the CRISPR endonuclease / cas9 is associated with an RNA fragment that suits him uniquely target genes, as being larger, the combination of A, T, C or G to less chance of ending up in many places of the genome. We can thus change targeted manner a gene in an organism such as pork.
The question remains as to when is the perfect GMO pig for xenotransplantation will be born!

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PhD Student in Biophysics

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