In vivo Gene Writing with engineered retrotransposons.

Engineered non-LTR retrotransposons, called Gene Writers, enable stable in vivo gene delivery of reporter and CAR-T genes in human cells and mouse models.

• Why it matters: Efficient in vivo integration of gene-length cargos remains difficult, limiting gene therapy applications. Addressing this gap could improve stable gene delivery methods for therapeutic use.
• What they did: A computational pipeline identified diverse non-LTR retrotransposons, which were extensively engineered to create Gene Writers capable of inserting reporter genes in human cells and generating CAR-T cells ex vivo and in vivo using lipid nanoparticle-mediated RNA delivery.
• The result: Gene Writers achieved robust, stable gene insertion and CAR-T cell generation with antitumor activity, enabling in vivo B cell depletion in a humanized mouse model and offering a framework for gene therapy advancements.