AAV-rh.74 Serotype

AAV capsid isolate designated rh.74, described as a serotype 8-like isolate. It packaged an AAV2-ITR vector with an MCK promoter and FLAG-tagged micro-dystrophin (labeled AAV8 in the study) that transduced skeletal muscle in rhesus macaques after intramuscular and intra-arterial delivery.

Length: 1 bp

Tropism: Skeletal muscle (rhesus macaque tibialis anterior and gastrocnemius; mouse tibialis anterior and diaphragm)

Characteristics

The cited study names the capsid once, as cap serotype 8-like isolate rh.74 in the production methods (HEK293 triple transfection), and calls the vector AAV8 elsewhere; all measurements were reported under the AAV8 label. At 5e12 vg per macaque tibialis anterior, 50.1 to 79.1% of fibers expressed micro-dystrophin.FLAG at 2 months and 37.6 to 54% at 5 months. Intra-arterial 2e12 vg/kg gave 82 and 89% transduction of gastrocnemius in seronegative macaques and 39 and 35% in two seropositive animals.

Applications: Delivery of FLAG-tagged micro-dystrophin to rhesus macaque skeletal muscle by intramuscular injection into tibialis anterior (followed up to 5 months) and by fluoroscopy-guided intra-arterial perfusion of gastrocnemius (3 months). In mdx mice, 1e11 vg gave 73.2% micro-dystrophin.FLAG-positive tibialis anterior fibers, and 2e11 vg injected into diaphragm protected against fatigue.

Limitations: The only cited study labels its vector AAV8, so rh.74-specific tropism outside muscle, human seroprevalence and liver or CNS behavior are not established by it. Pre-existing AAV8 antibodies (2 of 4 macaques) roughly halved gastrocnemius transduction, and all macaques made anti-AAV8 antibodies within weeks of dosing.

References

  1. Rodino-Klapac et al. (2009). Persistent expression of FLAG-tagged micro dystrophin in nonhuman primates following intramuscular and vascular delivery. Mol Ther - Rodino-Klapac 2009 AAVrh74 NHP

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