Table 1.
Muscle-directed gene transfer using rAAV vectors has been characterized in vertical translation studies from animal preclinical models to human clinical trials.
| Serotypes | Target issue/organ | Preclinical study in small animal models | Translational study in large animal models | Clinical trials |
|---|---|---|---|---|
| AAV1 | Skeletal muscle | Mouse [154] | Rabbit [157], cat [158] dog [36,96], NHP [32] | A1ATD [161], LGMD2D [162], LPLD [163] |
| Heart | Mouse [155] | Pig [159] | Heart failure [39] | |
| Rat [156] | Sheep [160] | |||
| Diaphragm | Mouse | Pompe disease [19] | ||
| AAV2 | Skeletal muscle | Mouse [164], Rat [165] | Dog [101], NHP [32] | A1ATD [169] |
| Hemophilia B [104] | ||||
| Heart | Mouse [155], Hamster [166] | Pig [168] | ||
| Rat [167] | ||||
| AAV5 | Skeletal muscle | Mouse [170] | ||
| Rat [171] | ||||
| AAV6 | Skeletal muscle | Mouse [172–174] | Dog [178] | |
| Heart | Mouse [175] | Dog [179, 180] | ||
| Rat [156, 176, 177] | Pig [181] | |||
| Sheep [182, 183] | ||||
| NHP [37] | ||||
| AAV7 | Skeletal muscle | Mouse [184, 185] | ||
| AAV8 | Skeletal muscle | Mouse [41, 186] | Dog [189, 190] | |
| Heart | Hamster [41] | NHP [191] | ||
| Mouse [41, 187] | NHP [37] | |||
| Hamster [41] | ||||
| Rat [188] | ||||
| AAV9 | Skeletal muscle | Mouse [42,47,192] | Dog [194] | |
| Heart | Mouse [43,47,56,188] | Dog [35] | ||
| Rat [188,193] | Pig [195] | |||
| NHP [37] | ||||
| AAV12 | Skeletal muscle | Mouse [196] | ||
| AAV2.5 | Skeletal muscle | DMD [34] |
A1ATD: α-1 anti-trypsin deficiency; AAV: Adeno-associated virus; DMD: Duchenne muscular dystrophy; LGMD2D: Limb-girdle muscular dystrophy type 2D; LPLD: Lipoprotein lipase deficiency; NHP: Nonhuman primate; rAAV: Recombinant adeno-associated virus.