Miniature and versatile genome regulation TnpB-ωRNA toolkits facilitate cancer immunotherapy - PubMed
7 hours ago
- #TnpB ωRNA toolkit
- #cancer immunotherapy
- #genome regulation
- The CRISPR-Cas systems are powerful for genome regulation but are limited by the large size of Cas proteins, hindering delivery via adeno-associated virus (AAV) for clinical use.
- Researchers engineered the IS200/IS605 transposon-encoded nuclease TnpB with its ωRNA scaffold to create an enhanced TnpB system, a compact toolkit for gene activation, genome editing, and base editing.
- The gene activator enTnpBa increases expression by 2889-fold using a minimized 93 nt ωRNA and robustly activates endogenous genes in mammalian cells.
- A single-AAV-based regimen called AAV-ImmunAct delivers enTnpBa to activate genes like CXCL9, IL-15, and IFN-γ, enhancing T cell migration, activation, and cancer cell killing.
- AAV-ImmunAct synergizes with anti-PD-1 therapy in humanized mice, establishing enTnpB as a promising compact platform for genome regulation and cancer immunotherapy.