Safety and Tolerability of the Adeno-Associated Virus Vector, AAV6.2FF, Expressing a Monoclonal Antibody in Murine and Ovine Animal Models
Abstract
:1. Introduction
2. Materials and Methods
2.1. AAV Vector Production
2.2. AAV Titration
2.3. Animal Experiments
2.4. Enzyme-Linked Immunosorbent Assays (ELISAs)
2.5. Hematology and Clinical Chemistry
2.6. Cytokine Analysis
2.7. Histology and Immunohistochemistry
2.8. AAV Vector Biodistribution
2.9. Statistics
3. Results
3.1. Confirmation of AAV6.2FF-31C2 Vector Expression
3.2. Safety and Tolerability of AAV6.2FF-31C2 in a Murine Model
3.3. Safety and Tolerability of AAV6.2FF-31C2 in a Pediatric Ovine (Sheep) Model
3.4. Lack of Pathology Observed in Murine and Ovine Models Following Intramuscular AAV-mAb Administration
3.5. Human IgG Is Expressed in Murine and Ovine Muscle
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Group | Cohort | Treatment | Dose (VG) | Endpoint | Number of Animals 2 |
---|---|---|---|---|---|
1 | Day 7-low | AAV6.2FF-31C2 | 1 × 1011 | Day 7 | n = 6 |
2 | Day 7-mid | AAV6.2FF-31C2 | 2 × 1011 | Day 7 | n = 6 |
3 | Day 7-high | AAV6.2FF-31C2 | 6 × 1011 | Day 7 | n = 6 |
4 | Day 7-mock | Vehicle only 1 | - | Day 7 | n = 6 |
5 | Day 28-low | AAV6.2FF-31C2 | 1 × 1011 | Day 28 | n = 6 |
6 | Day 28-mid | AAV6.2FF-31C2 | 2 × 1011 | Day 28 | n = 6 |
7 | Day 28-high | AAV6.2FF-31C2 | 6 × 1011 | Day 28 | n = 6 |
8 | Day 28-mock | Vehicle only 1 | - | Day 28 | n = 6 |
9 | Day 56-low | AAV6.2FF-31C2 | 1 × 1011 | Day 56 | n = 6 |
10 | Day 56-mid | AAV6.2FF-31C2 | 2 × 1011 | Day 56 | n = 6 |
11 | Day 56-high | AAV6.2FF-31C2 | 6 × 1011 | Day 56 | n = 6 |
12 | Day 56-mock | Vehicle only 1 | - | Day 56 | n = 6 |
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Rghei, A.D.; van Lieshout, L.P.; McLeod, B.M.; Pei, Y.; Lopes, J.A.; Zielinska, N.; Baracuhy, E.M.; Stevens, B.A.Y.; Thomas, S.P.; Yates, J.G.E.; et al. Safety and Tolerability of the Adeno-Associated Virus Vector, AAV6.2FF, Expressing a Monoclonal Antibody in Murine and Ovine Animal Models. Biomedicines 2021, 9, 1186. https://doi.org/10.3390/biomedicines9091186
Rghei AD, van Lieshout LP, McLeod BM, Pei Y, Lopes JA, Zielinska N, Baracuhy EM, Stevens BAY, Thomas SP, Yates JGE, et al. Safety and Tolerability of the Adeno-Associated Virus Vector, AAV6.2FF, Expressing a Monoclonal Antibody in Murine and Ovine Animal Models. Biomedicines. 2021; 9(9):1186. https://doi.org/10.3390/biomedicines9091186
Chicago/Turabian StyleRghei, Amira D., Laura P. van Lieshout, Benjamin M. McLeod, Yanlong Pei, Jordyn A. Lopes, Nicole Zielinska, Enzo M. Baracuhy, Brenna A. Y. Stevens, Sylvia P. Thomas, Jacob G. E. Yates, and et al. 2021. "Safety and Tolerability of the Adeno-Associated Virus Vector, AAV6.2FF, Expressing a Monoclonal Antibody in Murine and Ovine Animal Models" Biomedicines 9, no. 9: 1186. https://doi.org/10.3390/biomedicines9091186
APA StyleRghei, A. D., van Lieshout, L. P., McLeod, B. M., Pei, Y., Lopes, J. A., Zielinska, N., Baracuhy, E. M., Stevens, B. A. Y., Thomas, S. P., Yates, J. G. E., Warner, B. M., Kobasa, D., Fausther-Bovendo, H., Kobinger, G. P., Karimi, K., Thompson, B., Bridle, B. W., Susta, L., & Wootton, S. K. (2021). Safety and Tolerability of the Adeno-Associated Virus Vector, AAV6.2FF, Expressing a Monoclonal Antibody in Murine and Ovine Animal Models. Biomedicines, 9(9), 1186. https://doi.org/10.3390/biomedicines9091186