Human gene therapyOct 15, 2026

Using Mobile DNA and CRISPR-Based Tools Beyond Viruses for Genome Editing

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated Oct 16, 2026

Abstract

Clinical trials have shown feasibility for gene therapy using engineered cells, demonstrating sustained therapeutic effects through stable transgene integration.

Mobile genetic elements such as viruses, transposons, and retrotransposons offer distinct mechanisms for efficient gene delivery and genome modification.
Engineered systems like Sleeping Beauty and piggyBac DNA transposons support robust gene transfer for cell engineering.
R2 retrotransposon-based systems and CRISPR-associated transposons (CASTs) show potential for programmable insertion but remain in preclinical development.
Prime editing provides a method for precise sequence corrections without causing double-strand breaks, which may be beneficial for treating monogenic disorders.
The integration of these technologies highlights a progression from natural genome mobility to clinical genome engineering applications.

Simplified

Human gene therapy has been transformed by repurposing mobile genetic elements as tools for efficient gene delivery and precise genome modification. Viruses, transposons, and retrotransposons mobilize genetic material through distinct mechanisms with distinct advantages for genome engineering platforms with therapeutic potential. This review describes the mechanisms, performance characteristics, and translational relevance of nonviral methods of gene transfer and genome engineering, with emphasis on engineered systems such as the Sleeping Beauty (SB) and piggyBac (PB) DNA transposons, R2 retrotransposon-based platforms, CRISPR-associated transposons (CASTs), and prime editing (PE). Clinical trials using both SB- and PB-engineered cells have shown feasibility by demonstrating sustained therapeutic effect through stable transgene integration, such as CD19-directed CAR-T cell therapy for hematological malignancies. These transposon-based vectors enable robust gene transfer for cell engineering, but are fairly promiscuous with respect to where in the genome they insert their genetic cargo. On the contrary, R2-derived systems and CASTs represent promising technologies for programmable insertion, but are still under preclinical development. CRISPR-based PE provides a distinct route to precise sequence correction without double-strand breaks and is particularly attractive for the correction of monogenic disorders. Taken together, these technologies define a continuum from natural genome mobility to clinically relevant genome engineering. Continued optimization of delivery, targeting, and editing fidelity will determine how rapidly these approaches move from experimental innovation into routine clinical use.

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Using Mobile DNA and CRISPR-Based Tools Beyond Viruses for Genome Editing

Abstract

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