Topical gene therapy for the treatment of AP-1-associated genetic skin disorders

Quick Facts:
Tags: AP-1 transcription factor, Carcinogenesis, Combination therapy, Epidermis, Gene therapy, Genetic disorder, Homeostasis, Ichthyosis, Keratoderma, Palliative care, Protein targeting, Signal transducing adaptor protein, Topical medication, Wound healing
Inventors: Stephen Kaler, Tarun Kaniganti
Manager: Kristin Neuman
Departments: Pediatrics
Divisions: Columbia University Medical Center (CUMC)
Reference Number: CU26038
Release Date: 2026-02-26

This technology is a topical gene-delivery platform that restores functional subunits of the adaptor protein complex-1 (AP-1) in skin cells to treat monogenic genetic skin disorders such as ichthyosis and keratoderma.

Unmet Need: Disease-modifying treatments for monogenic genetic skin disorders

Current treatment strategies for severe inherited skin disorders, such as ichthyosis and keratoderma, involve palliative approaches that do not address underlying genetic and cellular defects. Existing gene therapy strategies for monogenic diseases are limited by risks of off-target effects, insertional oncogenesis, systemic exposure, and immune responses that prevent repeat administration. Consequently, there are no disease-modifying or curative treatments for patients with genetic skin disorders caused by defects in intracellular protein trafficking. Addressing these limitations is essential to enable safe, lasting correction of the molecular drivers of chronic skin diseases.

The Technology: Topical gene delivery platform for monogenic skin disease

This technology enables localized genetic correction in the skin by delivering functional gene sequences directly to epidermal cells through topical administration. Following application to affected skin areas, the delivery system transduces epidermal cells, introducing genetic material that supplements inherited deficiencies in intracellular protein trafficking pathways critical to epidermal development and maintenance. This localized approach confines gene delivery to diseased tissue, minimizing systemic exposure while supporting repeat administration for chronic conditions. By restoring key epidermal cellular functions, the approach is designed to support improvements in skin structure and barrier maintenance associated with inherited genetic defects, offering a safe, effective, and re-administrable gene therapy platform.

Applications:

  • Topical treatment of inherited skin disorders (ichthyosis, keratoderma, etc.)
  • Disease-modifying therapy for AP-1-associated genetic skin conditions
  • Localized gene delivery for chronic dermatologic diseases requiring repeat administration
  • Platform for topical gene therapy for monogenic skin disorders caused by intracellular trafficking defects
  • Research tool for studying epidermal protein trafficking and skin barrier homeostasis
  • Combination therapy with wound healing compounds

Advantages:

  • Localized gene delivery confined to diseased skin tissue
  • Safe, effective, and re-administrable gene therapy platform
  • Minimizes systemic exposure and off-target effects
  • Topical administration enables simple, non-invasive treatment
  • Expanded to multiple monogenic skin disorders through gene substitution

Lead Inventor:

Stephen Gerard Kaler, M.D.

Patent Information:

Patent Pending

Related Publications:

Tech Ventures Reference: