Nature communicationsMar 31, 2026

Small and flexible genome-editing tools help improve cancer immunotherapy

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

A compact TnpB-omegaRNA genome-regulation toolkit may help deliver AAV-based immune activation against cancer.

Evidence

This platform engineering study tested enTnpB and AAV-ImmunAct in mammalian cells, cancer cell lines, patient-derived organoids, and humanized mice.

Caveat

The immunotherapy evidence is preclinical, with no patient treatment outcomes reported.

Simplified

CRISPR‒Cas systems represent powerful tools for genome regulation. However, the large size of Cas proteins limits their efficient delivery via an adeno-associated virus (AAV), thereby restricting their clinical translation. Here, we engineer the IS200/IS605 transposon-encoded nuclease TnpB, along with its ωRNA scaffold, to create an enhanced TnpB system, which serves as a compact toolkit for gene activation, genome editing, and base editing. The gene activator enTnpBa increases expression by 2889-fold with a minimized 93 nt ωRNA and robustly activates endogenous genes in mammalian cells. We develop a single-AAV-based regimen for immune activation (AAV-ImmunAct) that delivers enTnpBa to activate CXCL9, IL-15, and IFN-γ. AAV-ImmunAct effectively enhances T cell migration and activation, increases killing of cancer cell lines and patient-derived organoids, and synergizes with anti-PD-1 therapy in humanized mice. Here, we establish enTnpB as a compact and versatile platform for genome regulation and a promising tool for cancer immunotherapy.

Full Text

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Small and flexible genome-editing tools help improve cancer immunotherapy

Abstract

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