Molecular editing to obtain biocompatible organs and tissues from animals.
The gap between the waiting lists of those in need of an organ and the number of organs actually available for transplantation is still very large and risks being exacerbated, in addition to the insufficient number of donations, by a very positive social trend: the gradual and steady decline in fatal road accidents. In recent decades, these terrible events have in fact been the main source of many organs suitable for transplantation, because they were removed from young, healthy people involved in fatal road accidents. Increased controls on alcohol abuse, public awareness campaigns and more efficient vehicles have all contributed to reducing the score of fatalities on the roads. This achievement risks, however, having a dramatic impact on those waiting for a liver or a heart to go on living.
A possible solution could come from the animal worldin the case of many tissues and organs such as corneas, heart, kidneys, animals and in particular pigs could be a valuable source of biocompatible organs.
There are, however, two major technical problems: the first is immune resistance on the part of the recipient organism to foreign tissues, and the second is related to diseases that can be transmitted through the implantation of tissues from different species.
Taking the pig as an example, which is the animal most often mentioned as a possible 'donor' because it has dimensions compatible with those of the human organism, the presence of retroviruses embedded in porcine DNA has been known for years. These are the so-called PERVs (Porcine Endogenous Retroviruses), whose genes are transmitted from one generation of pigs to the next, thus becoming an integral part of the porcine genome from which they can be synthesised and cause infections. The same happens in the human recipient organism in the case of xenotransplantation (transplantation between beings of different species).
A possible tool for deactivating retroviruses could come from genetic engineering: it is the CRISPR/Cas9a gene 'editing' technique derived from bacteria. In fact, CRISPRs are part of the bacteria's immune system and are also 'gene editors' thanks to the Cas endonuclease that recognises the RNA into which the viral DNA translates in order to replicate. The Cas enzyme takes over that RNA, so it recognises exactly the pieces of viral DNA and eliminates them all. The correction remains in the bacterium's genome and is passed on to the daughter cells.
Dr. Carmelo Chines
Direttore responsabile
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