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To address this, and increase the options for living implants in pediatric patients, we previously developed a lentiviral immune\u2010shielding strategy that leverages viral immune evasion mechanisms to downregulate surface HLA expression (via US2) and suppress natural killer (NK) cell activation (via Serpin b9). In this study, we comprehensively evaluated the impact of delivery of immune\u2010shielding genes in donor valve cells and whole donor valves on immune responses in vitro using host peripheral blood mononuclear cells (PBMCs). Our results demonstrate that this approach prevents immune cell\u2010mediated death of donor heart valve cells and reduces PBMC clustering around the allogeneic valve cells. Transcriptomic analysis of immune\u2010shielded donor valves via bulk RNA sequencing revealed upregulation of genes associated with immune tolerance pathways commonly observed in viral infections, cancer, and placental development. These findings support the impact of immune\u2010shielding technology as a strategy to protect allograft heart valves from immune\u2010mediated degeneration, advancing the path toward durable, immunologically compatible implants for pediatric patients.<\/jats:p>","DOI":"10.1002\/adhm.71737","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T11:15:59Z","timestamp":1789989359000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comprehensive In Vitro Profiling Demonstrates Successful Immune Evasion of Bioengineered Immune\u2010Shielded Heart Valves"],"prefix":"10.1002","author":[{"given":"Abraham van","family":"Wijk","sequence":"first","affiliation":[{"name":"Department of Paediatric Cardiothoracic Surgery, Wilhelmina Children's Hospital, Regenerative Medicine Center Utrecht University Medical Center Utrecht  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9893-8122","authenticated-orcid":false,"given":"Leanne Van den","family":"Berg","sequence":"additional","affiliation":[{"name":"Department of Paediatric Cardiothoracic Surgery, Wilhelmina Children's Hospital, Regenerative Medicine Center Utrecht University Medical Center Utrecht  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isa B. 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