Fig. 1.

AAV2/1 efficiently delivers antisense constructs to muscles. (A) Schematic representation of the mdx dystrophin mutation and of the AAV-U1#23 antisense construct. Antisense sequences complementary to the 5′ and 3′ splice sites of exon 23 (black bars) were cloned consecutively in the 5′ portion of U1 snRNA (black box). The corresponding antisense sequence is shown underneath the dystrophin pre-mRNA. (B) Muscle transduction after AAV2/1 systemic delivery. Green fluorescence was evident in several muscle districts 12 weeks after tail vein administration of 3–4 × 10¹² genome copies/mouse of AAV-U1#23. Intensively transduced fiber groups flank less or nonfluorescent muscle fibers possibly reflecting heterogeneous perfusion inside the muscle. Heart and diaphragm are also widely transduced although to a lower level than voluntary striated muscle.