Optimization & Further Development of the iPhAGE System

Recent advancements in the iPhAGE platform have led to further optimizations, resulting in improved transduction capabilities and reduced immunogenicity.

Key Enhancements:

• Vector Minimization: Streamlined genetic constructs to eliminate non-essential sequences, thereby reducing vector size and potential off-target effects.

• Ligand Display: Incorporation of specific cell-targeting ligands on the phagemid surface to facilitate targeted delivery to desired cell types.

• Enhanced Stability: Structural modifications to improve vector stability during production and storage, ensuring consistent performance.

These optimizations collectively contribute to a more efficient and targeted gene delivery system, reinforcing the potential of the iPhAGE system for therapeutic applications.

Optimization and Applications of the M13 iPhAGE System:

The M13 iPhAGE system is now the focus of further development due to its potential to package and deliver ssDNA and linear covalently closed DNA minivectors, theoretically limitless gene cargo capacity, and highly modifiable ligand display allowing for efficient cell-type specific targeting.

iPhAGE Applications: Present Studies & Future Investigations

• Neuronal applications:

  • Astrocyte reprogramming as part of Pillar 2 of the iNeuron Project

  • Neuronal targeting for Alzheimer’s disease

• Retinal applications:

  • Photoreceptor targeting for Stargardt’s disease

    • This system has demonstrated the ability to package large genes associated with many retinal-related eye diseases, including the 6.8 kbp ABCA4 gene implicated in Stargardt disease

• Epidermal applications:

  • Fibroblast targeting for COL1A1 delivery for possible cosmetic applications or COL7A1 for therapeutic applications for Epidermolysis bullosa