Summary Table: Skin / Epithelial-Specific Promoters

Promoter	Target Cell Type	Size (bp)	Origin	Key Characteristics
K14 (Keratin 14)	Basal Keratinocytes	~0.8 – 2.0 kb	Human	Targets the innermost (basal) layer of the epidermis. Ideal for long-term expression as these cells are progenitors.
K5 (Keratin 5)	Basal Keratinocytes	~1.0 – 2.2 kb	Human / Mouse	Functionally similar to K14; these two keratins form the primary cytoskeleton of the basal layer.
Involucrin (hINV)	Differentiated Keratinocytes	~0.5 – 2.0 kb	Human	Specific to the suprabasal layers. Active only as cells begin to mature and move toward the skin surface.
E-cadherin (CDH1)	General Epithelial	~0.6 – 1.5 kb	Human	A “pan-epithelial” marker. Active in most epithelial sheets, including skin, gut, and lung linings.

Insights into Skin-Directed Vectors

1. Longevity and the Basal Layer (K14/K5) If a transgene is delivered to the outer layers of the skin, it will be shed within weeks due to natural skin turnover. To achieve permanent or long-term correction, researchers use K14 or K5 promoters. These target the basal keratinocytes, which stay attached to the basement membrane and continuously divide, ensuring the transgene is passed on to daughter cells.

2. Involucrin for “Layer-Specific” Therapy Involucrin is a marker of terminal differentiation. This promoter is particularly useful if the goal is to express a protein specifically in the barrier layer of the skin (the stratum corneum). It is often used in models of psoriasis or ichthyosis, where the pathology is located in the upper epidermal layers.

3. E-cadherin: The Epithelial “Glue” E-cadherin is essential for cell-cell adhesion. While it is highly active in the skin, it is not “skin-exclusive” like K14; it will also drive expression in the lining of the colon and kidneys. It is often used in studies of Epithelial-to-Mesenchymal Transition (EMT) in cancer research to track or target stable epithelial populations.

4. Topical vs. Viral Delivery Because the skin is easily accessible, these promoters are frequently used in Lentiviral vectors for ex vivo gene therapy (correcting patient skin cells in a dish and then grafting them back) or in AAV5/AAV9 for direct intradermal injection.