Gene Humanized Mice: HUGO-GT™ Full-Length Human Gene Replacement

Cyagen's HUGO-GT™ (Humanized Genomic Ortholog for Gene Therapy) platform provides precisely engineered humanized mice by replacing both the entire coding sequence (CDS) and introns of a mouse gene with its full-length human counterpart, and in many models extends humanization to the 5′ and 3′ UTRs. Unlike simple cDNA insertions or randomly integrated transgenes, this preserves the native mouse promoter and critical regulatory elements, so the human gene is expressed in the right tissues, at physiological levels, under authentic control, providing the basis for reliable disease modeling and translational drug evaluation.

This genomic architecture makes HUGO-GT™ humanized mouse models particularly valuable for sequence-dependent therapies that require a gene match. ASOs, siRNAs, and guide RNAs for gene editing act by base pairing, and a candidate optimized against the human transcript will not engage the mouse ortholog. Retaining human introns, splice regulatory elements, and UTRs means splice-switching and exon-skipping ASOs, 3′UTR-targeting siRNAs, and base or prime editing can be evaluated with the actual clinical candidate rather than a mouse surrogate. The same models support AAV and LNP gene therapy, human-specific antibodies and small molecules, target validation, and in vivo efficacy, PK/PD, and safety studies, all on a defined background, generated by proprietary TurboKnockout™ technology.