We are excited to announce that we are now offering large genomic humanizations up to 240 kb by the replacement of a murine gene with its human orthologue. This new technology is called ‘Ozgene Big Genomic Replacement’ – or OzBIG for short. This new capability is a result of several experimental projects with a 100% success rate to date.

Large genomic replacements allow for the complete humanization of most genes and the expression of the human gene from its accompanying cis-regulatory elements. They have multiple valuable applications in the medical research field. OzBIG can also be used  to build large non-humanized, transgenics like complex reporters and synthetic expression systems.

OzBIG vastly expands the gene set available for humanisation by enabling the humanisation of 90% of the genes in the mouse genome, compared to 10% with standard gene targeting. OzBIG combines conventional gene targeting technology with a screening platform developed at Ozgene to efficiently generate ES cell clones carrying modifications with a current upper limit of 240 kb without the use of exogenous recombinases like CRISPR.

Mice carrying large genomic humanizations can be useful as models of human genetic disease as well as in the development of corrective gene therapies. Models containing human genomic sequences with clinically relevant mutations can be used as experimental targets for the application of Cas9-based prime editing technologies to correct genomic mutations for the treatment of human genetic disease.

Genomic humanizations also permit the expression of a full-length humanized transcript that can be useful for the study of therapeutic agents aimed at treating genetic human diseases by correcting defects in transcript splicing, modulating transcript levels or by altering the transcription or regulation of RNA.

These large genetic modifications also allow for humanizing multiple linked genes and/or large modifications, such as the addition of reporters or conditional elements.

What are humanized mice?

Humanized mice broadly refer to mouse models expressing human genes via transgenesis to gain relevant insights in the in vivo context for the understanding of human-specific physiology and pathology. Whilst many basic biological insights have been obtained from mouse studies, there are limitations to animal models when investigating human biology. There are components of mouse biology systems that are inconsistent with their human counterparts, particularly the human immune system. Humanized mouse models have begun to fill this gap and have become important pre-clinical tools for biomedical research. The use of humanized mice may facilitate the application of customised treatment in the medical industry.