AAVmyo Serotype

Peptide-displaying AAV9 capsid variant (AAV9P1) carrying the 7-mer peptide P1 (RGDLGLS) on the capsid surface. Identified in a barcoded in vivo screen of 183 pre-selected capsids in mice. Transduces skeletal muscle, diaphragm and heart after intravenous injection, with lower liver transduction than AAV9.

Length: 1 bp

Tropism: Skeletal muscle (quadriceps femoris, biceps), diaphragm, heart (mouse, intravenous)

Origin: AAV9 capsid with the P1 peptide inserted in variable region VIII

Characteristics

After intravenous injection of 1e11 vg of CMV-eyfp vectors into C57BL/6 mice, eyfp mRNA is 61-fold (diaphragm), 17-fold (quadriceps femoris) and 11-fold (heart) higher than with AAV9 and 9-fold lower in liver (1 week). With SPc5-12-driven firefly luciferase (4e10 vg, CB17-SCID mice, 4 weeks), mRNA is 11.6-fold (diaphragm), 37.8- to 50.1-fold (skeletal muscles) and 5.8-fold (heart) higher than AAV9 and 23.2-fold lower in liver. Titers are comparable to AAV9, and the capsid is compatible with affinity-column purification.

Applications: Intravenous gene delivery to skeletal muscle, diaphragm and heart in mice (C57BL/6 and CB17-SCID). Micro-dystrophin from AAVMYO is expressed at higher levels than from AAV9 in quadriceps of mdx mice 4 weeks after 2e11 or 1e12 vg per mouse. Transduces type I, IIa and IIb muscle fibers in quadriceps femoris.

Limitations: Tested in mice only; the cellular receptor is unknown, and the RGD motif in P1 suggests integrin binding as a hypothesis. Also transduces white fat in a subset of mice. The P504A/G505A liver-detargeted variant AAVMYO_LD is less active in muscle. Fold-changes versus AAV9 vary with mouse strain and dose.

References

  1. Weinmann et al. (2020). Identification of a myotropic AAV by massively parallel in vivo evaluation of barcoded capsid variants. Nat Commun - Weinmann 2020 AAVMYO

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