Genetic Models

APOL1 Portfolio—Humanized Mouse Models for APOL1‑Mediated Kidney Disease (AMKD)

De-risk APOL1 drug development with genotype-specific models

Selecting the right APOL1 model is critical to demonstrating efficacy, safety, and translational relevance in APOL1‑targeted drug development. Taconic’s portfolio of humanized APOL1 mouse models enables sponsors to align genotype with development stage:

  • G0 — baseline biology and on-target safety
  • G1 — proof-of-concept efficacy
  • G2 — robustness and failure-risk assessment

Most APOL1 programs require a combination of reference (G0) and risk-variant (G1 or G2) models to support confident translational decisions.

Which APOL1 model should I use? 

Development questionRecommended model
Baseline biology / on-target safety13022 (G0)
Proof-of-concept efficacy13175 (G1)
Genotype robustness / severity13017 (G2)
Translational or regulatory-grade studyG0 + G1 or G2

Why humanized APOL1 models are required

Because APOL1 is absent in rodents, model selection—not compound potency—is often the limiting factor in translation.Conventional mouse models cannot capture APOL1-specific biology or therapeutic response. Humanized models are therefore required to evaluate APOL1-targeted mechanisms.

Taconic’s humanized APOL1 models:

  • Express human APOL1 under physiologically relevant control
  • Enable study of risk‑variant–specific kidney injury
  • Support evaluation of direct APOL1-targeted modalities, including small molecules, antisense oligonucleotides (ASOs), and RNA-based approaches
  • Are compatible with inflammatory, stress-based, or combinatorial “second-hit” paradigms

These models align with the mechanistic hypotheses and endpoints currently being advanced in clinical development.

APOL1 Model Portfolio

Model 13022

Humanized APOL1 G0 (Reference)

Purpose: Baseline biology and on-target safety

This model expresses the non-risk (G0) human APOL1 allele and serves as a critical reference control for APOL1 drug development programs.

 

Recommended applications:

  • On-target safety and tolerability assessment
  • Differentiating disease-driven effects from mechanism-driven effects
  • Comparator arm for G1 and G2 efficacy studies
  • Pharmacodynamic benchmarking of APOL1 modulation

Why it matters:
Supports interpretation of on-target effects and is often included in studies intended to inform translational and regulatory decisions.

View Humanized APOL1 G0 (Reference)
Grey silhouette of cryopreserved mouse

Model 13175

Humanized APOL1 G1

Purpose: Proof-of-concept efficacy

This model expresses the APOL1 G1 risk variant, the most prevalent APOL1 risk allele observed in patient populations.

 

Recommended applications:

  • Proteinuria reduction studies
  • Evaluation of APOL1 channel inhibitors or gene-silencing approaches
  • Inflammatory or interferon-based second-hit paradigms
  • Early efficacy ranking of therapeutic candidates

Why it matters:
This model is typically the primary entry point for APOL1 efficacy studies and represents a clinically relevant starting point for most programs.

View Humanized APOL1 G1
Grey silhouette of cryopreserved mouse

Model 13017

Humanized APOL1 G2

Purpose: Genotype robustness and severity testing. This model expresses the APOL1 G2 risk variant, which is associated with high-risk kidney disease phenotypes.

 

Recommended applications:

  • Genotype-specific efficacy comparisons (G1 vs G2)
  • Durability of response and chronic dosing studies
  • Stress-testing therapeutic robustness across APOL1 variants
  • Advanced preclinical packages supporting IND-enabling studies

Why it matters:
Used to stress-test therapeutic performance and identify failure risk, strengthening translational confidence across APOL1 genotypes.

View Humanized APOL1 G2
Grey silhouette of cryopreserved mouse

Supported therapeutic modalities

  • These models are validated for evaluation of APOL1-targeted approaches currently advancing in clinical development, including:
  • Small-molecule APOL1 channel inhibitors
  • Antisense oligonucleotides (ASOs)
  • RNA-based knockdown or modulation approaches
  • Combination regimens with standard-of-care therapies (e.g., RAAS or SGLT2 inhibitors)
  • These models can also be combined with inflammatory or surgical paradigms to explore multi-hit mechanisms of kidney injury.

Cardiometabolic Diseases Portfolio

Explore Taconic's cardiometabolic disease portfolio, including validated mouse models for obesity, MASH, diabetes, and dyslipidemia. Access study-ready cohorts, custom diet conditioning, and in vivo phenotyping services to accelerate your preclinical research.
View Cardiometabolic Disease Mouse Models
Cardiometabolic Disease Portfolio

Partner with Taconic

Taconic’s APOL1 portfolio combines genetically engineered models with translational study design expertise.

Contact us to design an APOL1 study aligned with your program goals.