CRISPR/Cas and dermatology: A new era of skin treatment modalities

Summary: Abstract Body: CRISPR/Cas has accelerated gene editing capabilities and holds tremendous potential in dermatology; however, many potential dermatology applications have not been comprehensively explored. This study examines current applications and identifies ideal dermatologic candidates for future CRISPR/Cas therapies. We conducted a literature review of studies involving CRISPR/Cas in dermatology using keywords “[CRISPR],” “[dermatology],” “[gene therapy],” “[genetic skin disease],” “[delivery],” “[skin disorder],” “[caspase],” “[Cas],” “[antimicrobial]”, “[virus],” “[CRISPR-Cas9]”, “[CRISPR/Cas9]”, and “[history]” in the PubMed database. We identified 62 articles relevant to current and potential CRISPR/Cas dermatology applications. Across five monogenic dermatoses, two inflammatory conditions, four cutaneous infections, and two malignancies, CRISPR/Cas has been effective in correcting genetic mutations, reducing inflammation, and disrupting pathogenic processes. It has corrected genetic mutations in multiple forms of epidermolysis bullosa through the DNA repair mechanisms homology-directed repair and non-homologous end joining to restore dermal-epidermal adhesion and inactivate pathogenic alleles. CRISPR/Cas9 has also reduced inflammation in atopic dermatitis and psoriasis by targeting NLRP3 via microneedle patches. CRISPR/Cas knockout has disrupted viral oncogenes in human papillomavirus and Kaposi’s sarcoma herpesvirus, reduced tumor growth in cutaneous squamous cell carcinoma, and enhanced immune targeting in metastatic melanoma. Recent CRISPR/Cas innovations, such as lipid nanoparticles for topical delivery and prime editing for precise single-base substitutions, are further broadening the scope of CRISPR/Cas gene editing applications. These findings highlight the significant progress that CRISPR/Cas has made in the field of dermatology. As ongoing research refines its applications and addresses safety considerations, CRISPR/Cas will further transform future treatment possibilities for genodermatoses and a wide range of dermatologic conditions. Jonathan C. Hwang², Richard B. Brown², Edra Ha², Joe Tung¹ 1. Dermatology, UPMC, Pittsburgh, PA, United States. 2. University of Pittsburgh School of Medicine, Pittsburgh, PA, United States. Genetic Disease, Gene Regulation, Gene Therapy & Epigenetics