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Dr. David Diaz-Carballo

Dear all,
My current works are focused on human endogenous retroviruses (HERVs) in cancer. Something like Paleovirology. We have discovered some new elements which are non-truncated and biologically active in tumors. In HIV infection by the way, they are transactivated and perhaps contribute to the general problem in HIV persistence. A couple of thoughts: I think that targeting host proteins like DDX3 might provide more success in disabling the transcriptional activation of HIV. Recently, a team from Italy and Spain created a molecule which target this cell structure and they eliminated four viruses at once. They published these results in PNAS (http://www.pnas.org/content/early/2016/04/21/1522987113). We are working on this in relation to cancer as well. We ablate the CXCR4 receptor from cancer cells (solid and hematological tumors) very efficiently. We are employing right now the system Alt-crRNA:tracr from the company IDT (USA and the Flanders in Belgium) with success to disable several HERVs and CXCR4 as well. This system deliver the RNP-complexes very well. Regarding the possible malfunctions in the cytokines network and cell homing in case of ablation of both CXCR4 and CCR5 receptors, I can tell you that both scenarios are not incompatible with life. In fact for CXCR4 it is already known in medicine what happens in individuals with somatic mutations on this receptor: the WHIM-Syndrome (https://de.wikipedia.org/wiki/WHIM-Syndrom). The other one CCR5 do not represent a treat in case of mutations. Perhaps, because the cytokines are rather promiscuous than monogamous in their functions.
In regard to the delivery of gRNAs in all possible compartments of the body, I agree that the viral vectors like AVV are a good thing. But to be honest, I have the tendency to support the ex vivo modifications of cells and their systemic diffusion. It is a practicable thing, given that the fact that all transplants in leukemia and lymphoma restore the bone marrow using this approach with highly success. Moreover, the amplification of cells in vitro is a practicable, cheaper and functional technique.
David Diaz-Carballo

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