Engineered Retrotransposons Called Gene Writers Insert Gene-Length DNA From an RNA Template, Including to Make CAR-T Cells In Vivo in Mice

Preclinical study (cells and mouse model) · CellNovember 1, 2026 · 1 min read · Dr. Abdelmuhsen Abusneina

Schematic: an engineered non-LTR retrotransposon and an RNA template carrying a gene, supplied in trans, insert gene-length cargo at a target site in the genome of a human cell — A generic illustration of the approach (prepared for this brief, not a figure from the paper). The paper names target-primed reverse transcription as the mechanism; details are in the full paper.

Putting a whole gene into a chosen place in the genome is still hard, especially inside the body. A team at Tessera Therapeutics now reports that retrotransposons, natural genetic elements that copy themselves through an RNA intermediate, can be engineered into a tool for this, which they call Gene Writers.

The problem

Efficient insertion of gene-length cargo in vivo remains difficult. Non-LTR retrotransposons naturally move large DNA segments through an RNA intermediate, which makes them a candidate for carrying genes, but they had not been developed into a general tool.

What the authors did

They built a computational pipeline to identify a diverse set of non-LTR retrotransposons and then engineered them extensively. The result is elements that insert reporter genes efficiently and stably in human cells using RNA templates introduced in trans, that is, supplied separately from the enzyme.

What they reported

Gene Writers were used to make CD19 and CD20 chimeric antigen receptor (CAR) T cells ex vivo, and these cells showed robust antitumor activity. When the RNA was delivered with lipid nanoparticles, the system generated CAR-T cells in vivo and produced stable B cell depletion in a humanized mouse model. The authors describe a framework for discovering, engineering and applying non-LTR retrotransposons and say it bridges a gap among existing gene therapy approaches.

Schematic of the applications reported: Gene Writers inserted reporter genes in human cells, generated CD19 and CD20 CAR-T cells ex vivo with antitumor activity, and, with RNA delivered in lipid nanoparticles, generated CAR-T cells in vivo with stable B cell depletion in a humanized mouse model — The applications as listed in the abstract (illustration prepared for this brief, not a figure from the paper). The abstract gives no quantitative results.

Why it matters

Making CAR-T cells inside the body, instead of collecting and engineering a patient's cells in a laboratory, is an active goal in cell therapy. The report adds a way to insert a gene-sized cargo using RNA that can be packaged in lipid nanoparticles, the same class of carrier discussed in the brief on lipid nanoparticle design.

Keep in mind

The abstract gives no numbers: no insertion efficiency, no measure of antitumor activity or B cell depletion, no durability, and no information on where in the genome the cargo lands or on off-target insertions. The in vivo work is in a humanized mouse model, not in people. Nearly all authors are affiliated with Tessera Therapeutics. Safety, specificity and delivery to relevant tissues would need to be shown before any clinical use.

Original paper

Paper: Li D, De Iaco A, Ngan KC, et al. In vivo Gene Writing with engineered retrotransposons. Cell. 2026. Published October 21, 2026.
Type: Preclinical study in human cells and a humanized mouse model
DOI: 10.1016/j.cell.2026.09.054
PubMed: PMID 42906542

KeywordsGene therapy Lipid nanoparticles RNA therapeutics CAR-T cells Retrotransposons

Abdelmuhsen Abusneina, PhDAssociate Professor
Research focus: Molecular Oncology and Cancer Metabolism
Department of Molecular Diagnostics, Faculty of Biomedical Sciences, University of Benghazi, Libya

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