Gene Therapy and Dermatological Disorders

Gene therapy is a novel and promising approach for treating various diseases caused by genetic defects or mutations. Gene therapy involves introducing a functional gene or gene product into target cells or tissues to correct or compensate for defective genes or to modulate gene expression. Dermatological disorders encompass a group of skin diseases that impact the appearance, function, and health of the skin and its appendages. These disorders can be categorized into three groups: inherited, acquired, and neoplastic. Some of these conditions result from genetic abnormalities affecting the structure or function of the skin, such as epidermolysis bullosa, ichthyosis, and albinism. Others are caused by environmental factors, immune dysregulation, or malignancy, including psoriasis, vitiligo, and melanoma. Gene therapy holds promise in treating dermatological disorders by addressing underlying genetic defects or modulating the immune response or cell cycle.

Characteristics of Gene Therapy for Dermatological Disorders

One of the main characteristics of gene therapy for dermatological disorders is the diversity of gene delivery methods available for transferring therapeutic genes into skin cells or tissues. Gene delivery methods can be broadly classified into two categories: viral and non-viral. Viral vectors are modified viruses capable of infecting target cells and delivering the desired gene into the cell nucleus. Viral vectors offer high transfection efficiency and long-term expression, but they also have drawbacks, such as immunogenicity, toxicity, insertional mutagenesis, and limited gene size. Commonly used viral vectors for dermatological disorders include retroviruses, lentiviruses, adenoviruses, adeno-associated viruses, and herpes simplex viruses. Non-viral vectors are synthetic or natural molecules that can bind to the target gene and transport it across the cell membrane. Non-viral vectors exhibit low immunogenicity, low toxicity, a large gene capacity, and ease of production. However, they also have limitations, including low transfection efficiency and short-term expression. Commonly used non-viral vectors for dermatological disorders include liposomes, polymers, nanoparticles, plasmids, and electroporation. Another characteristic of gene therapy for dermatological disorders is the possibility of ex vivo gene transfer. This approach involves isolating skin cells or tissues from the patient or a donor, modifying these cells or tissues with the therapeutic gene in vitro, and then transplanting them back to the patient. Ex vivo gene transfer offers advantages over in vivo gene transfer, such as avoiding systemic side effects, enhancing gene expression, and allowing for quality control. However, it also faces challenges such as maintaining cell viability, preventing graft rejection, and managing infection risk.

Research and Clinical Progress of Gene Therapy for Dermatological Disorders

Gene therapy for dermatological disorders has made rapid progress in recent decades, with several preclinical and clinical studies demonstrating its feasibility and efficacy in treating various skin diseases. The following summarizes current research or clinical progress in gene therapy for common or rare dermatological disorders, such as epidermolysis bullosa, melanoma, psoriasis, and vitiligo.

Table 1. Research and Clinical Progress of Gene Therapy for Dermatological Disorders

Dermatological Disorder Gene Therapy Approach Achievement
Epidermolysis bullosa (EB) Ex vivo gene-corrected autologous keratinocytes Retroviral vector encoding laminin 5-α3 subunit
Lentiviral vector encoding type VII collagen Long-term correction of recessive dystrophic EB in a mouse model
Ex vivo gene-modified allogeneic fibroblasts Adeno-associated viral vector encoding type VII collagen
Melanoma Adenoviral vector encoding tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) Regression of metastatic melanoma lesions in patients
Plasmid encoding interleukin-12 (IL-12) Enhancement of anti-tumor immunity in patients
Nanoparticles delivering small interfering RNA (siRNA) targeting vascular endothelial growth factor (VEGF) Inhibition of tumor growth and angiogenesis in a mouse model
Psoriasis Plasmid encoding vascular endothelial growth factor receptor 2 (VEGFR2) Suppression of psoriatic lesions in patients
Liposomes delivering siRNA targeting cyclooxygenase-2 (COX-2) Reduction of inflammation and proliferation in a mouse model
Plasmid encoding aquaporin-3 (AQP3) Improvement of skin barrier function and hydration in a mouse model
Vitiligo Plasmid encoding basic fibroblast growth factor (bFGF) Repigmentation of vitiligo patches in patients
Nanoparticles delivering siRNA targeting tyrosinase-related protein 1 (TYRP1) Prevention of depigmentation in a mouse model
Ex vivo gene transfer of plasmids encoding stem cell factor (SCF) Induction of melanocyte differentiation and migration in vitro

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For research use only. Not intended for any clinical use.