Selecting appropriate models for non-clinical studies of gene therapies

A review by The Cell and Gene Therapy Catapult sets out the key factors that should be considered when selecting an animal model to be used in non-clinical studies for adeno-associated virus (AAV) based gene therapies.

Selecting appropriate models for non-clinical studies of gene therapies

Currently, six AAV-based gene therapies have been approved in the UK, including treatments for spinal muscular atrophy and haemophilia, with many more experimental therapies being developed.

Before testing an experimental gene therapy in human clinical trials, a developer is currently required by the regulatory authorities to demonstrate that their product is both safe and effective in animal studies. It is vital that developers select an appropriate animal model for these studies as this helps them to ethically and optimally gather the data that is needed to progress to human clinical trials.

In this review, published in Gene Therapy, the non-clinical team at Cell and Gene Therapy Catapult provide guidance on four factors that developers should consider when selecting an animal model to test AAV-based gene therapies. These factors are:

  • The pharmacological activity of the intended clinical product in the animal model. The non-clinical studies should be performed with the most pharmacologically relevant animal model available.
  • The animal permissivity for the chosen AAV serotype. The AAV vector must be able to circumvent the immune system and function in a similar manner in both the animal species and humans.
  • The capability of the AAV to infect the target cells and tissues.
  • The physiology of the animal model. If the model does not possess a similar physiological target that is found in humans, it will be challenging to translate the data from the animal models into information relevant for potential future clinical trials.