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Selection of appropriate non-clinical animal models to ensure translatability of novel AAV-gene therapies to the clinic

Abstract

Gene Therapy Medicinal Products consist of a recombinant nucleic acid intended for the modulation or manipulation of a genetic sequence. A single administration of a novel gene therapy has the potential to be curative, with a durable long-term benefit to patients. Adeno-associated viral vectors have become the viral vector of choice for in vivo delivery of therapeutic transgenes as they are mildly immunogenic, can effectively transduce a variety of human tissues and cells, and have low levels of genomic integration. Central to the effective translation of data generated in discovery studies to the clinic is the selection of appropriate animal species for pivotal non-clinical studies. This review aims to support the selection of appropriate animal models for non-clinical studies to advance the development of novel adeno-associated virus gene therapies.

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Fig. 1: Animal model selection.

Data availability

There was no data used in this study. All sources of information for this review were found in currently published literature and are referenced accordingly.

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Acknowledgements

MS would like to thank Dr. Bhatnagar for useful conversations about the manuscript.

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No specific funding was obtained for the writing of this manuscript. This was undertaken as part of the tasks assigned to Mark Singh and his colleagues at The Cell and Gene Therapy Catapult.

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Singh, M., Brooks, A., Toofan, P. et al. Selection of appropriate non-clinical animal models to ensure translatability of novel AAV-gene therapies to the clinic. Gene Ther 31, 56–63 (2024). https://doi.org/10.1038/s41434-023-00417-x

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