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We are revolutionizing the translational potential of animal models in preclinical research. Discover the latest articles and news about our recent activities.

Bridging the translational gap: Humanized Liver models as predictive tools for RNA therapeutic success

The field of RNA therapeutics, with its potential for treating a wide range of diseases, continues to experience rapid growth and attracts significant investment. According to the American Society of Gene & Cell Therapy (ASGCT), as of Q1 2025, 35 RNA therapies have been approved globally and another 1,298 are currently in development (between preclinical and pre-registration stages) [1].

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Bridging the Gap

Humanized Liver Models: Revolutionizing RNA Therapeutic Development

The rapid growth of RNA therapeutics, including siRNA and mRNA, is transforming the pharmaceutical and medical landscape, offering unprecedented potential for treating diseases ranging from viral infections to metabolic disorders. Despite this promise, translating these groundbreaking treatments from the lab to the clinic is fraught with challenges.

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Humanized Liver PXB-Mouse

PXB-mouse: Overcoming species-to-species differences to accurately predict hepatotoxicity in therapeutic development

It is estimated that 40% of drug candidates have failed to make it to market because of toxicity.¹ One of the most common adverse drug reactions is drug-induced liver injury (DILI), whereby patients experience acute illness, often with symptoms similar to hepatitis and cholestasis. Today, DILI is the leading cause of drug candidate failure and post-market withdrawals.² The high incidence of DILI in clinical trials, and even post-market events, is partly due to the use of conventional animal models at preclinical stages. Conventional models are notoriously poor predictors of efficacy and toxicity in the liver, due to species-to-species variation. In contrast, the PXB-mouse® model, with its humanized liver, provides a highly predictive model of human physiology and human-specific hepatotoxicity, allowing for more accurate prediction of human outcomes, and, therefore, aiding the smooth progression of new therapeutics into the clinic.

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Setting up HBV studies for human translational success

Hepatitis B is a serious and globally prevalent disease with 296 million people worldwide living with chronic hepatitis B virus (HBV) infections. Recent advances in HBV therapeutics have made infection a treatable disease, but they only disrupt certain areas of the HBV lifecycle. As a result, if the therapeutics are withdrawn, patients can relapse. What’s more, long-term use can cause antiviral resistance. To cure the disease, therapeutics need to address every stage of the HBV lifecycle, providing both seroclearance of the hepatitis B surface antigen (HBsAg) and silencing of the genomically integrated HBV DNA. However, investment in this space carries considerable risk as developers struggle to move treatments from animal models to human studies. Notably, human responses to HBV therapies are notoriously difficult to predict and traditional animal models translate poorly to the human environment, causing significant delays, as well as safety, cost, and efficacy concerns.

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Selecting the best model for preclinical hepatitis studies

How can humanized liver models provide accurate efficacy measurements at each stage of the viral lifecycle? Hepatitis B is a serious global health threat. Around 1.5 million hepatitis B virus (HBV) infections were identified in 2019 alone and around 296 million people are thought to be living with the chronic disease.¹ Researchers are now targeting previously unexplored areas of the viral lifecycle to get closer to developing a complete cure.

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How PXB-mice with humanized livers enable better translational outcomes for gene-based therapeutics

In recent years, we have seen an explosion in the number of adeno-associated virus (AAV) vector-based gene therapies progressing to clinical trial stages, and subsequently an increasing number of regulatory successes. The reasons for this are clear. The versatility of AAV-based platforms makes them prime technology for targeting a range of tissues and pathologies, through their ability to silence, replace or modify genes.

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