Limb Perfusion Delivery of a rAAV1 Alpha-1 Antitrypsin Vector in Non-Human Primates Is Safe but Insufficient for Therapy
Our results suggest that clinically effective AAT gene therapy may ultimately require delivery at doses between 3.5 × 10<sup>13</sup>-1 × 10<sup>14</sup> vg/kg, which is within the dose range used for approved rAAV gene therapies. Muscle-targeting strategies could be incorporated when delivering systemic administration of high-dose rAAV gene therapies to increase transduction of muscle tissues and reduce the burden on the liver, especially in diseases that can present with hepatotoxicity such as AAT deficiency.
Authors
- T. F. Gallagher (ORCID: https://orcid.org/0000-0001-6381-6902)
- Terence R. Flotte (ORCID: https://orcid.org/0000-0002-8255-0588)
- Allison M. Keeler (ORCID: https://orcid.org/0000-0002-5202-4616)
- Janet M. Benson (ORCID: https://orcid.org/0000-0001-9599-8122)
- Qiushi Tang
- Alisha M. Gruntman (ORCID: https://orcid.org/0000-0003-4818-8391)
- Meghan Blackwood (ORCID: https://orcid.org/0000-0002-3051-6548)
- Kristin Vyhnal (ORCID: https://orcid.org/0000-0002-9086-4165)
- Darcy Reil
- Jessica A. Chichester (ORCID: https://orcid.org/0000-0001-7879-120X)
- Debora Pires-Ferreira
- Jane A. Lindborg
- Dongtao Fu
Institutions
- Lovelace Respiratory Research Institute (US)
- University of Massachusetts Chan Medical School (US)
- University of Florida (US)
- Biomedical Research Institute (US)
- NeuroNexus (United States) (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- Genes
- Published
- 2024-09-10
- DOI
- https://doi.org/10.3390/genes15091188
- Primary Topic
- Virus-based gene therapy research
- Type
- article
- Field-Weighted Citation Impact
- 0.00