Current Projects, Gene Therapy, Quality of Life Change
About This Project

A nanoneedle bandage for topical intracellular COL7A1 gene therapy to accelerate wound healing in Recessive Dystrophic Epidermolysis Bullosa

Lay summary

This project develops a new approach to improve and speed up the healing of skin wounds in patients with Recessive Dystrophic Epidermolysis Bullosa (RDEB). The aim is to use a bandage decorated with nanoscale (tiny) needles as a dressing for the wounded skin area, in order to inject the functional version of the Collagen VII gene (COL7A1) directly inside the cells in the wound, while maintaining the skin protection.

Because the nanoneedles inject COL7A1 directly inside cells, instead of being delivered through the circulation or applied on top of the skin, the gene is safe from being inactivated by the mechanisms present in the body that fight the invasion by foreign entities (e.g. immune system, enzymes that degrade nucleic acids). In this way, the direct injection into the cells can produce more functioning Collagen VII for a longer time, while using less COL7A1, making the wound healing treatment more efficient, more affordable, less invasive, and less frequent.

In prior work, the nanoneedles have already successfully delivered COL7A1 to cells from patients with RDEB. This project is developing a strategy to place the nanoneedles on a flexible bandage and test whether this bandage is safe and effective in an animal model, preparing the way for clinical trials.

Scientific Summary

RDEB is a debilitating skin disease caused by loss-of-function COL7A1 gene mutations. Severe forms of the disease can manifest chronic wounds that progress to debilitating scars and join contractures.

This project aims to develop the nanoneedle bandage as a painless, simple and rapid approach to delivery functional COL7A1 genes to blistered/eroded skin in order to accelerate skin healing. We envision applying the bandage to affected areas, to deliver genes intracellularly over a prolonged time, restoring the integrity and mechanical stability of the dermal-epidermal junction.

The GMP-level toolbox necessary for nanoneedle transfection of RDEB cells with COL7A1 has been developed. The next aim is to generate a flexible nanoneedle substrate and use it to conformally deliver COL7A1 to skin wounds in a mouse model, to optimise safety and efficiency. Once optimised, the effectiveness of the NanoCol topical gene delivery strategy at promoting wound healing will be tested, validating this approach for patients.

Related Publications

Mustfa, S.A., et al. Nanomedicine Approaches to Negotiate Local Biobarriers for Topical Drug Delivery Adv. Therap. 2021, 4:2000160