1. Volume 16, Issue 4, Pages 665-672 (April 2008)
AAV Vector-mediated Reversal of Hypoglycemia in Canine and Murine Glycogen Storage Disease Type Ia 
Dwight D Koeberl, Carlos Pinto, Baodong Sun, Songtao Li, Daniel M Kozink, Daniel K Benjamin, Amanda K Demaster, Meghan A Kruse, Valerie Vaughn, Steven Hillman, Andrew Bird, Mark Jackson, Talmage Brown, Priya S Kishnani, Yuan-Tsong Chen 
Molecular Therapy 
Volume 16, Issue 4, Pages (April 2008)
DOI: /mt
Copyright © 2008 The American Society of Gene Therapy Terms and Conditions

2. Figure 1
Prolonged survival in glucose-6-phosphatase (G6Pase) (–/–) mice following adeno-associated viral (AAV) vector administration. Affected mice did not survive until 1 month of age, unless the AAV vector was administered at 12 days of age. (a) Proportion of G6Pase (–/–) mice surviving following administration of the indicated number of AAV2/8 vector particles (vp): 1 × 1013/kg (1E+13; n = 6), 1 × 1012/kg (1E+12; n = 11), 3 × 1011/kg (3E+11; n = 12), 1 × 1011/kg (1E+11; n = 6), or no vector (n = 5). (b) Weight of wild-type mice and G6Pase (–/–) mice following administration of the indicated number of AAV2/8 vp: 1E+13 (n = 6), 1E+12 (n = 11), 3E+11 (n = 9), or untreated wild-type mice (n = 6). (c) Proportion of G6Pase (–/–) mice surviving following administration of the indicated number of AAV2/1 vp: 1E+13 (n = 8), 3E+13 (n = 6), or untreated wild-type mice (wild type; n = 5). (d) Blood glucose following a 2-hour fast for wild-type mice and G6Pase (–/–) mice following administration of the indicated number of AAV2/8 vp: 1E+13 (n = 6), 1E+12 (n = 11), 3E+11 (n = 9), untreated G6Pase (–/–) mice (n = 7), or wild-type mice (n = 4). (e) Blood cholesterol for the mice in d. (f) Urine organic acid analysis from G6Pase (–/–) and wild-type mice following administration of the indicated number of vp at the indicated ages. AAV, adeno-associated virus.
Molecular Therapy  , DOI: ( /mt )
Copyright © 2008 The American Society of Gene Therapy Terms and Conditions

3. Figure 2
Prolonged survival and correction of hypoglycemia in glycogen storage disease type Ia (GSD-Ia) dogs following AAV2/8 vector administration. (a) Kaplan–Meier survival of GSD-Ia dogs following AAV2/8 vector (1 × 1013 vp/kg) administration at 3 days of age (AAV2/8, n = 3), and GSD-Ia dogs maintained by carbohydrate supplementation alone (untreated, n = 6). (b) Blood glucose following a 2-hour fast at the indicated ages. (c) Blood levels of cholesterol, triglycerides, and lactate following a 2-hour fast at 1 month of age. AAV, adeno-associated virus.
Molecular Therapy  , DOI: ( /mt )
Copyright © 2008 The American Society of Gene Therapy Terms and Conditions

4. Figure 3
Correction of glucose-6-phosphatase (G6Pase) deficiency in the liver of G6Pase (–/–) mice following adeno-associated viral (AAV) vector administration. Analysis of G6Pase (–/–) and wild-type mice following administration of the indicated number of vector particles (vp) at the indicated ages. Mean ± SD are shown. (a) Liver G6Pase activity quantitated as the degradation of G6P. Wild-type untreated mice (n = 5); G6Pase (–/–) mice following administration of AAV2/8 (1E+13, n = 4; 1E+12, n = 4, 3E+11, n = 5), or AAV2/1 (1E+13, n = 4); or G6Pase (–/–) untreated (n = 4). (b) Liver glycogen content quantitated as the release of glucose for the mice in a. (c) Weight of liver and kidney, shown as the ratio to body weight for the mice in a.
Molecular Therapy  , DOI: ( /mt )
Copyright © 2008 The American Society of Gene Therapy Terms and Conditions

5. Figure 4
Reversal of biochemical abnormalities in glycogen storage disease type Ia (GSD-Ia) dogs following AAV2/8 vector administration. (a) Liver glucose-6-phosphatase (G6Pase) activity quantitated as the degradation of G6P. (b) Liver glycogen content quantitated as the release of glucose. Mean ± SD are shown. AAV, adeno-associated virus.
Molecular Therapy  , DOI: ( /mt )
Copyright © 2008 The American Society of Gene Therapy Terms and Conditions

6. Figure 5
Reversal of glycogen and lipid accumulations in the liver of glucose-6-phosphatase (G6Pase) (–/–) mice and glycogen storage disease type Ia (GSD-Ia) dogs following AAV2/8 vector administration. Representative images are shown (three samples were evaluated for each image shown). (a) Periodic acid-Schiff staining for glycogen and histochemical detection of G6Pase in G6Pase (–/–) mouse liver at 26 weeks of age following administration of the indicated number of AAV2/8 vector particles (vp). (b) Oil red O staining for GSD-Ia dog liver at 4 months of age following vector administration (1E+13 vp/kg), or 1 month of age (untreated). Lipid vacuoles indicated (arrows). Original magnification ×200. (c) Western blot detection of hepatocyte growth factor (HGF) in the liver of G6Pase (–/–) mice or (+/+) littermates (Wildtype). Vector-treated mice [(–/–), AAV] received the AAV2/8 vector (1 × 1013 vp/kg). Each lane represents an individual mouse. Western blot of α-tubulin is shown to demonstrate equivalent loading of each sample. AAV, adeno-associated virus.
Molecular Therapy  , DOI: ( /mt )
Copyright © 2008 The American Society of Gene Therapy Terms and Conditions