https://video.igem.org/videos/watch/134a1a9e-7285-40cc-a7a0-362ef85f4c13 Title: IGNITE Description: This is the presentation video of iGEM team HBUT‑China, introducing their project IGNITE. It develops a living tumor therapeutic based on engineered oHSV‑2 oncolytic virus armed with AI‑optimized Neo‑IL‑2, to reprogram MSS colorectal cancer from “cold tumors” into “hot tumors”. Inspired by a clinical interview with a cancer patient’s family member — “We are not afraid of treatment. What we fear is that treatment hurts more than the disease itself” — the team set effective and tolerable as their core design principle. Accounting for 85% of advanced colorectal cancer cases, MSS tumors have a 5‑year survival rate below 15% and are typical immune‑cold tumors. Conventional chemoradiotherapy damages healthy tissues, while immune checkpoint inhibitors and CAR‑T show limited therapeutic benefits for such patients. The team adopted a dual‑mechanism strategy: “oncolytic virus plus immune activator”. oHSV‑2 selectively replicates and lyses tumor cells, yet monotherapy yields unsatisfactory outcomes. Native IL‑2 activates effector immune cells but triggers excessive expansion of suppressive Treg cells and severe systemic toxicity. Therefore, the team engineered IL‑2 to preserve IL‑2Rβγ signaling and reduce binding to IL‑2Rα. In the dry‑lab phase, the team used structural biology tools and AI generative models, and built the in‑house ProVarFlow evaluation platform for a dry‑wet‑lab closed loop. Five variants were shortlisted from 100 candidate sequences. The first‑round variant 3 failed expectations, showing that lowered IL‑2Rα affinity alone was insufficient. After the second iteration, variant 2 passed plasmid construction, virus packaging and purification. Validated by flow cytometry, SPR and other assays, variant 2 fulfilled design requirements and was named Neo‑IL‑2. Subsequent quality‑control tests, in‑vitro killing assays and mouse‑model experiments preliminarily confirmed the anti‑tumor potency of the recombinant virus. As a standardized basic part, Neo‑IL‑2 was submitted to the iGEM Registry. Its modular design enables reuse by other groups, with full sequences, modeling and experimental data publicly available. Attaching great importance to biosafety, the team built the SHIELD safety framework and adopted a double‑knockout safe viral backbone under BSL‑2 standards. They co‑authored an open‑access bilingual biosafety manual with four other iGEM teams, and standardized animal ethics and lab management protocols. The HOPES human‑practice framework incorporates feedback from patients, clinicians, researchers and safety experts to drive project iteration. Under the SAME education framework, outreach activities include 3D‑printed teaching models, virtual labs, inclusive science courses for disadvantaged groups, bilingual picture books and online lectures, popularizing synthetic biology and cancer prevention knowledge. The team cooperated with Binhui Biotech for clinical translation and took part in domestic and international synthetic‑biology events. Every engineering decision originates from real clinical demands. Going forward, the team will further refine this therapy, hoping to deliver effective, well‑tolerated cancer treatments to more patients. Wiki | Official Page Thu, 29 Oct 2026 22:24:50 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/134a1a9e-7285-40cc-a7a0-362ef85f4c13 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.