Preclinical Development and Safety of Laterally Spreading Dual AAV.SPR-MYO7A Vectors for the Treatment of Usher Syndrome Type 1B

ATSN-301, a dual AAV.SPR vector reconstituting full-length MYO7A in macaque retina, was well tolerated in a 6-month GLP toxicology study with a NOAEL of 1.2E11 vg/eye.

• Why it matters: Usher syndrome type 1B has no approved treatment for progressive retinitis pigmentosa, and MYO7A exceeds AAV packaging limits, creating a need for safe retinal gene delivery.
• What they did: The team engineered dual AAV hybrid/overlap platforms with optimized cDNA split points and reduced non-coding sequence, then used laterally spreading AAV.SPR capsids to drive smCBA-promoter expression in cynomolgus macaques.
• The result: In macaques, AAV.SPR enabled supraphysiological MYO7A expression at macular and distal retinal sites without foveal detachment, and GLP toxicology showed tolerability at all doses, supporting clinical advancement.

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