A human organ platform to replace animal models in gene therapy testing

Severe genetic liver diseases affect more than a million people worldwide. These illnesses are rare but serious, and they happen when a single gene in the liver doesn’t work properly. Gene therapy—which aims to fix or replace the faulty gene—could offer life‑changing treatments. But, before these therapies can be given to patients, they must be tested to check that they are both effective and safe.

This is usually done in animals, often by genetically altering mice.

Teresa’s project involves testing gene therapy directly in diseased human livers, using machine-perfusion to keep the organs alive outside the body. Machine perfusion is already part of standard care in NHS transplant centres, where it is used to keep donor organs alive outside the body by circulating warm, oxygen‑rich blood.

Teresa has already pioneered the adaptation of this technology for research, transforming otherwise discarded human organs into highly physiological, ex vivo disease models.

Now, she wants to find out if they can be used for testing new gene therapies.

Teresa hopes to demonstrate that machine-perfusion human livers faithfully reproduce genetic liver disease phenotypes, respond predictably to gene therapy, and enable human-relevant toxicity testing at clinically meaningful doses.

These findings will provide a robust, clinically translatable alternative to animal models for preclinical gene therapy research, using patient tissue that would otherwise have been discarded.

Developing new treatments for medical conditions should ideally always be done using models that mirror human physiology. Using human organs directly is  not often possible, but this project represents a real opportunity to make the most of real human tissue donated by real patients, while also replacing animals.