TnpB Nuclease, The Ultra-Compact RNA-Guided Nuclease Redefines Precision Genome Editing

KACTUS, in collaboration with AstraGenomics, is proud to introduce TnpB Nuclease: a new generation, ultra-compact RNA-guided nuclease discovered through metagenomic mining. With its small size, high purity, robust editing efficiency, and exceptional fidelity, TnpB Nuclease is set to become a powerful new asset for cell and gene therapy, agricultural biotechnology, and beyond.

High Purity: The Foundation of Reliable Editing

Consistent gene editing starts with high purity. Through optimization of TnpB Nuclease’s sequence and production process using our proprietary SAMS™ platform, KACTUS achieves >90% purity, ensuring reliable performance in every application.

Figure 1. Bis-Tris PAGE analysis shows TnpB Nuclease purity >90%

Figure 2. SEC-HPLC analysis confirms TnpB Nuclease purity >90%

High Editing Efficiency: Especially for Gene Knock-In

Efficient DNA cleavage is essential and TnpB delivers. In vitro assays demonstrate that TnpB Nuclease effectively cleaves double-stranded DNA substrates to generate the expected products (Figure 3).

In cellular knockout experiments (Figure 4), TnpB achieved high-efficiency disruption of endogenous genes, including KLKB1, TTR, and TET2 in HEK293T cells, and ANGPTL3 in Hepa1-6 cells, validating its broad applicability across cell types and targets.

Figure 3. TnpB nuclease efficiently cleaves dsDNA substrates in vitro

Figure 4. TnpB nuclease enables high-efficiency gene knockout in HEK293.

Most notably, TnpB excels in gene knock-in applications, a critical yet challenging task in therapeutic development. In primary human T cells activated for CAR-T engineering, TnpB mediated >90% knockout at the TRAC locus, while achieving >60% CAR+ expression via homology-directed repair (HDR) (Figure 5). This dual efficiency, precise cutting plus high knock-in rates, makes TnpB uniquely suited for editing hard-to-transfect primary cells, offering a superior solution for CAR-T/CAR-NK cell therapy, large-fragment integration, and other complex editing scenarios.

Figure 5. In activated primary T cells, TnpB enables >90% TRAC knockout and >60% CAR+ expression at the TRAC locus.

High Fidelity: Precision You Can Trust

For clinical translation, specificity is paramount. Comprehensive off-target profiling (Figure 6) confirms that TnpB exhibits significantly lower off-target activity and higher on-target specificity than other commonly used nucleases. This stems from its stringent requirement for perfect complementarity, especially in the seed region, where even a single mismatch abolishes cleavage. The result true precision: efficient on-target editing without compromising genomic integrity.

Figure 6. TnpB demonstrates significantly lower off-target effects compared to other editors (TnpB belongs to the AG Editors family)

Powering the Future of Genome Engineering

KACTUS remains deeply committed to advancing the gene editing toolbox for cell and gene therapy. Our strategic partnership with AstraGenomics merges cutting-edge discovery with industrial-scale production, continuously expanding access to innovative editing platforms.

With its ultra-compact size, high activity, and exceptional fidelity, TnpB Nuclease unlocks new possibilities for precise therapeutic cell engineering.

Product Information

TnpB Nuclease is now available: Click here for more details.