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The New York Times article Gene Editing Spurs Hope for Transplanting Pig Organs Into Human links to the recent Science publication Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9 Niu et al. Science 10 Aug 2017: eaan4187, DOI: 10.1126/science.aan4187.

The highlighted section of the abstract says "...we inactivated all the PERVs in a porcine primary cell line..." where a PERV is a porcine endogenous retrovirus, an RNA virus which carries its own reverse transcriptase molecule and converts to DNA before incorporating into the host's genome.

Question: Do they mean to say all currently known PERVs or is there some way to be absolutely sure that every PERV in the pig's genome is known. In other words, could they have missed one? Could there be an as-yet unidentified PERV? I don't really want to ask about the possibility of an entirely new and unknown class of retroviruses; rather I'm trying to understand how all PERVs as currently defined can be identified in a pig cell line.

The reason that this is important is that the motivation here is to generate pig organs for transplantation into humans. The concern is that the pig genome may contain retroviruses that could then infect the human host, and the further possibility that it could be passed infectiously to others. As pig to human infectious disease is always a concern, starting with a "clean" pig genome is of particular epidemiological importance.

The first sentence of the NYTimes article:

In a striking advance that helps open the door to organ transplants from animals, researchers have created gene-edited piglets cleansed of viruses that might cause disease in humans. (emphasis added)

Abstract of Niu et al. 2017:

Xenotransplantation is a promising strategy to alleviate the shortage of organs for human transplantation. In addition to the concern on pig-to-human immunological compatibility, the risk of cross-species transmission of porcine endogenous retroviruses (PERVs) has impeded the clinical application of this approach. Earlier, we demonstrated the feasibility of inactivating PERV activity in an immortalized pig cell line. Here, we confirmed that PERVs infect human cells, and observed the horizontal transfer of PERVs among human cells. Using CRISPR-Cas9, we inactivated all the PERVs in a porcine primary cell line and generated PERV-inactivated pigs via somatic cell nuclear transfer. Our study highlighted the value of PERV inactivation to prevent cross-species viral transmission and demonstrated the successful production of PERV-inactivated animals to address the safety concern in clinical xenotransplantation. (emphasis added)

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You are right, they should have written "all currently known PERVs". Although the structure of ERVs is generally well understood (https://www.ncbi.nlm.nih.gov/pubmed/26104559; https://www.ncbi.nlm.nih.gov/pubmed/26818261) there may be some complex cases that have been missed. Also, the map of the porcine genome is not fully complete yet (nor the human one) so you cannot be sure that there are no ERV-derived sequences hidden in the unsequenced regions.

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  • $\begingroup$ More intriguing than I realized Sequences derived from ERVs make up at least 8 to 10% of the human and mouse genomes and range from ancient sequences that predate mammalian divergence to elements that are currently still active Mager & Stoye, and "Despite state-of-the-art genomic tools available for retroviral discovery and the large number of retroviral sequences described to date, there are still gaps in understanding retroviral macroevolutionary patterns and host-retrovirus interactions and a lack of a coherent systematic classification particularly for HERVs" Escalera-Zamudio & Greenwood $\endgroup$ – uhoh Aug 11 '17 at 10:19

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