Progress in skin gene therapy: From the inside and out

Area of Science:

• Dermatology
• Regenerative Medicine
• Genetic Therapy

Background:

• The skin acts as a crucial barrier, protecting internal organs from external damage.
• Genetic skin disorders often require palliation due to treatment challenges.
• Cellular and gene therapies present promising avenues for treating severe genetic skin conditions.

Purpose of the Study:

• To examine current cell and gene therapy approaches for genetic skin disorders.
• To discuss delivery strategies from both external (topical, intradermal, transdermal) and internal (systemic) perspectives.
• To use recessive dystrophic epidermolysis bullosa (RDEB) as a model to illustrate therapeutic applicability.

Main Methods:

• Review of existing cell and gene therapy strategies for skin applications.
• Analysis of 'outside-in' approaches: topical, intradermal, and transdermal delivery, including ex vivo cell expansion and grafting.
• Analysis of 'inside-out' approaches: systemic delivery via infusion for skin benefit.

Main Results:

• Delivery across the skin's barrier to subdermal compartments remains a significant challenge.
• Both localized and systemic delivery methods show potential for treating genetic skin disorders.
• Ex vivo cell expansion and grafting represent a key external delivery strategy.

Conclusions:

• Cell and gene therapies hold significant promise for treating genetic skin disorders.
• Overcoming the skin's barrier function is critical for effective therapeutic delivery.
• Recessive dystrophic epidermolysis bullosa serves as a valuable model for advancing these therapies.