Life Science

ADME/Tox Partnerships

Partners in ADME/Tox
Sigma® Life Science is building partnerships with the goal of creating novel ADME/Tox cell based assays. By applying the CompoZr® ZFN technology, we can partner to develop unique screening tools tailored to your pre-clinical testing needs.

We are partnering with companies to create novel and unique assays for the areas of:

  • Drug Metabolism
  • Drug Safety
  • Genetic Toxicology
  • Developmental and Reproductive Toxicology

If you are interested in discussing developmental partnership opportunities for these or other areas of interest with Sigma Life Science, please contact us at admetox@sial.com.

Or fill out the ADME/Tox Partnership Request Form.

Predictive Tools for pre-clinical testing
With Sigma Life Science’s exclusive rights to CompoZr ZFN technology we can genetically modify most cell lines. Within the ADME/Tox focus of research, we can:

  • Knockout any gene/target in cell line of interest
  • Create reporter-based assay systems using endogenous or external promoters
  • Modify endogenous genes (e.g. polymorphisms, site-directed mutations)
  • Assess the biologic function of any gene or pathway
  • Boost or retain physiologically relevant genes

Project Types

Genetically Engineered Cell Line Projects

Figure 1. Examples of genetically engineered cell line projects that are possible with CompoZr ZFN technology.

Cell Design Studio

Sigma Life Science is leveraging the Cell Design Studio to engineer new cell based assays specific to our partner’s needs. Utilization of the Cell Design Studio puts our expertise and technologies to work for our partnership. Together we will create novel and unique assays that will lead to more predictive results and help to bring safer drugs to market, faster.

Project Phases
CDS projects are divided into phases.

Project Phases

Project Example

Objective: Disrupt tetraploid ABCG2 gene in C2BBe1 cells (a Caco2 derived subclone) in order to eliminate function of BCRP efflux transporter.

Genotype Analysis
Homozygous knockout (no functional protein)

  • 4 base pair deletion
  • 5 base pair insertion

WT:
AGGAGATCAGCTACACCACCTCCTTCTGTcatcaACTCAGATGGGTTTCCAAGCGTTC

Allele 1&2:
AGGAGATCAGCTACACCACCTCCTTCTGT----aACTCAGATGGGTTTCCAAGCGTTC

Allele 3&4:
AGGAGATCAGCTACACCACCTCCTTCTGTcGTCATatcaACTCAGATGGGTTTCCAAGCGTTC

Phenotype Analysis
BCRP efflux disrupted

Efflux Ratio of Substrates

Figure 2. The transport of Digoxin, CDCFDA, and Estrone-3-Sulfone (E3S) in C2BBe1 BCRP knockout cells.
The Efflux Ratio (B-A/A-B) of the MDR1 substrate, Digoxin, the MRP2 substrate, CDCFDA, and the BCRP substrate, Estrone-3-Sulfone (E3S), was measured in the C2BBe1 BCRP knockout cell line and the wildtype C2BBe1 cell line. As can be seen in the Figure below, the efflux ratio for E3S is eliminated in the BCRP knockout cell line, whereas, the efflux ratio for digoxin and CDCFDA remains unaffected.

For more information on starting a developmental partnership with Sigma Life Science, please contact us at admetox@sial.com.

Or fill out the ADME/Tox Partnership Request Form.

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