Key Takeaways

  • OCT-guided nonviral delivery enabled targeted opsin gene expression in degenerating retinal tissue

  • Treated mice demonstrated sustained visual responses through 52 weeks, while a focal injury model showed functional recovery within 1 week

  • The investigational platform may support localized treatment of retinal degeneration but requires human evaluation

Nanoscope Therapeutics announced the publication of preclinical findings demonstrating that an optical coherence tomography (OCT)-guided, nonviral gene delivery platform enabled targeted opsin gene expression and sustained visual responses in mouse models of retinal degeneration.

The study, published in Frontiers in Pharmacology, evaluated the company's investigational nano-enhanced optical delivery (NOD) platform, which combines PEGylated plasmonic gold nanorods with low-power near-infrared laser light to deliver multi-characteristic opsin (MCO)-encoding plasmids into inner retinal neurons.

The approach uses OCT imaging to guide gene delivery to specific retinal regions affected by photoreceptor loss, potentially addressing challenges associated with localized degeneration in geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

In rd1 mice, a model of severe photoreceptor degeneration, OCT-guided delivery produced robust MCO expression in inner retinal cells without disrupting retinal structure or altering retinal thickness. Treated mice demonstrated significantly greater electroretinography and visually evoked potential responses than untreated controls, with responses sustained through 52 weeks.

Researchers also evaluated the platform in a focal laser-injury model designed to mimic GA. Localized MCO delivery restored microfocal electroretinography responses in the damaged retinal region within one week of treatment. Biodistribution testing at 12 months showed vector DNA levels in evaluated nonocular tissues comparable to those in controls.

According to Nanoscope, the platform's nonviral design could accommodate larger genetic payloads, including gene-editing constructs, without the packaging-size limitations associated with viral vectors.