Volume 20, Issue 10, Pages (October 2012)

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Volume 20, Issue 10, Pages 1863-1870 (October 2012) Balloon Catheter Delivery of Helper-dependent Adenoviral Vector Results in Sustained, Therapeutic hFIX Expression in Rhesus Macaques Nicola Brunetti-Pierri, Aimee Liou, Priti Patel, Donna Palmer, Nathan Grove, Milton Finegold, Pasquale Piccolo, Elizabeth Donnachie, Karen Rice, Arthur Beaudet, Charles Mullins, Philip Ng Molecular Therapy Volume 20, Issue 10, Pages 1863-1870 (October 2012) DOI: 10.1038/mt.2012.143 Copyright © 2012 The American Society of Gene & Cell Therapy Terms and Conditions

Figure 1 Plasma hFIX levels in rhesus macaques. Vector was administrated on day 0. Normal; >30% of normal. Mild; >5–30% of normal. Moderate; ≥1–5% of normal. Severe; <1% of normal. Normal hFIX level is ~5,000 ng/ml. Molecular Therapy 2012 20, 1863-1870DOI: (10.1038/mt.2012.143) Copyright © 2012 The American Society of Gene & Cell Therapy Terms and Conditions

Figure 2 Serum ALT and AST levels in rhesus macaques. Normal range for ALT is 5–61 U/l. Normal range for AST is 12–63 U/l. Grade 1 (mild) = 1.1–2.5× upper limit of normal (ULN). Grade 2 (moderate) = 2.6–5.0× ULN. Grade 3 (severe) = 5.1–10× ULN. Grade 4 (potentially life-threatening) >10× ULN. ALT, alanine transaminase; AST, aspartate transaminase. Molecular Therapy 2012 20, 1863-1870DOI: (10.1038/mt.2012.143) Copyright © 2012 The American Society of Gene & Cell Therapy Terms and Conditions

Figure 3 Levels of total anti-hFIX antibodies and inhibitors in rhesus macaques. Vector was administered on day 0. BU, Bethesda units. Molecular Therapy 2012 20, 1863-1870DOI: (10.1038/mt.2012.143) Copyright © 2012 The American Society of Gene & Cell Therapy Terms and Conditions

Figure 4 Plasma hFIX levels in mice. Mice injected with two different preparations (lot no. 040908 or lot no. 102308) of HDΔ21.7E4gE-hFIX at 1 × 1012 virus particle/kg. N = 5 per group. Mean ± SD shown. Molecular Therapy 2012 20, 1863-1870DOI: (10.1038/mt.2012.143) Copyright © 2012 The American Society of Gene & Cell Therapy Terms and Conditions

Figure 5 Vector biodistribution in rhesus macaques. Vector genome copies were determined by real-time PCR in different organs in rhesus 17664, 17633, and 18407. Molecular Therapy 2012 20, 1863-1870DOI: (10.1038/mt.2012.143) Copyright © 2012 The American Society of Gene & Cell Therapy Terms and Conditions