Penn Medicine research offers promising insights into AAV-based gene therapies' safety: Integration into human DNA is unlikely to trigger cancer mutations.
A recent study from the University of Pennsylvania’s Gene Therapy Program, published in Nature Biotechnology and Human Gene Therapy, analyzed AAV-based gene therapies in non-human primates. This study suggests that the integration of AAV vectors into chromosomal DNA, if it occurs, is unlikely to induce cancer-causing mutations in humans. These findings could alleviate previous concerns about the safety of adeno-associated viral vectors in gene therapy.
The study also highlights a key strategy for achieving stable, long-term expression of therapeutic genes delivered via AAV vectors. The research team explored various molecular pathways involved in AAV integration and found that while integration events do occur, they do not appear to disrupt critical genetic regions that could lead to cancer. Instead, the study demonstrates that these events might help enhance the therapeutic effects of gene therapy by promoting sustained gene expression in target cells, such as liver cells, without raising significant cancer risks.
Short video describing how Adeno-associated Viral Vectors work in gene therapy
(Media source: https://www.youtube.com/watch?v=raM8q7eTmgM)
Furthermore, the researchers discovered that AAV integrations might offer more than just safety. By integrating into non-coding regions of the genome, these vectors may actually increase the long-term effectiveness of the therapy. This unexpected finding opens up new avenues for gene therapy strategies, where controlled integration could be harnessed to extend the benefits of treatment while keeping safety as a top priority.
This research sheds light on the future of AAV-based gene therapies, offering a deeper understanding of how AAV transgene expression can be consistently maintained in patients. Additionally, it helps pave the way for further developments in genetic treatments for a variety of disorders, potentially making gene therapies safer and more durable over time.
Read more about these findings here:
Created: March 1st, 2024
Citation:
Greig, J.A., Martins, K.M., Breton, C. et al. Integrated vector genomes may contribute to long-term expression in primate liver after AAV administration. Nat Biotechnol (2023). https://doi.org/10.1038/s41587-023-01974-7
Kelly M.M., Camilo B., Qi Z., Zhe Z., Caitlin L., Jenny A.G., and James M.W. Prevalent and Disseminated Recombinant and Wild-Type Adeno-Associated Virus Integration in Macaques and Humans. Human Gene Therapy (2023). https://doi.org/10.1089/hum.2023.134
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