Homologous Recombination

Gene targeting technology for humanized, Knockin & conditional Knockout models

Homologous recombination is a genetic recombination in which nucleotide sequences are exchanged between two similar or identical DNA molecules.

It is commonly applied in mouse genetics. Also called gene targeting, this method can be used to specifically replace a copy of a gene by integrating a gene different from that of origin.

Of therapeutic interest are the creation of Knockout mice using embryonic stem cells to deliver artificial genetic material in order to repress the target mouse gene.

Furthermore, this technology enables a robust and efficient Knockin of a particular mutation, reporter, or human gene sequence into endogenous loci, leading to accurate and physiologically more relevant human disease models.

Such models show significant impact on research experiments and drug development programs spanning activities from target validation to ADMET studies.

Typical mouse model creations using homologous recombination

Humanization of Target Genes such as:

• Cell membrane receptors for compound testing
• Cell membrane molecules for in vivo evaluation of antibodies and biologics
• Soluble molecules (Ig, transport proteins, interleukins, and hormones)

Monitoring of Biomarker Expression in order to:

• Detect early events in response cascades
• Quantify physiological responses

Monitoring of Off-Target Effects in order to:

• Determine and quantify non-specific activities
• Measure induction or repression of biomarker

Labeling for Cell Trafficking by:

• Insertion of biomarker in any cell-specific gene to monitor a cell lineage or a subpopulation of a cell lineage

Models for Translational Medicine in order to:

• Efficiently mimic human diseases or drug side effects
• Improve xenograft efficacy

Tissue-Specific Transgene Expression in order to:

• Determine transgene expression pattern and level of expression

Target Validation & Knockout Models in order to

• Monitor gene deletion efficacy and validate the reliability of the model