https://video.igem.org/videos/watch/0527854f-3f01-4922-a1ad-8c7cf804dbdd Title: MOCHI - Making OCH1 Controlled Humanization Inducible Description: Turning a gene down, at an exact moment of your choice is a very valuable tool. We use RNA interference, a natural mechanism of gene regulation that lowers the production of a target protein by repressing translation of the complementary mRNA. Our work builds on Ruan et al. (2025), who showed that RNAi can be established in Komagataella phaffii by introducing the Argonaute 1 enzyme from Naumovozyma castellii together with a double-stranded RNA precursor. That publication also points to a limitation: the silencing may weaken over time. Our proposed solution is creating a stronger dsRNA signal by introducing a RNA dependent RNA polymerase that constantly supplies new dsRNA molecules. We want to achieve this by introducing QDE-1 ΔN from Neurospora crassa. The result we hypothesize to be more templates for further silencing and the creation of a self-enhancing loop. One possible target is OCH1, the gene that initiates yeast-type hypermannosylation and thereby stands in the way of therapeutic proteins with human-like glycosylation. Only about 20% of monoclonal antibodies worldwide are sold outside the United States, Europe and Canada, and even in high-income countries their price is one reason for unequal access; the major cost driver is production in mammalian CHO cells. Producing antibodies in yeast could make these medicines cheaper and more accessible. Throughout the year we found more applications for our RNAi cycle. This video follows the project from the origin paper through our experimental design and results, and shows how conversations outside the lab shaped the system we built. Wiki | Official Page Thu, 29 Oct 2026 22:25:28 GMT https://validator.w3.org/feed/docs/rss2.html PeerTube - https://video.igem.org https://video.igem.org/client/assets/images/icons/icon-1500x1500.png https://video.igem.org/videos/watch/0527854f-3f01-4922-a1ad-8c7cf804dbdd All rights reserved, unless otherwise specified in the terms specified at https://video.igem.org/about and potential licenses granted by each content's rightholder.