Topical gene editing therapeutics using lipid nanoparticles: “gene creams” for genetic skin diseases?

Abstract

Abstract Patients living with inherited skin diseases have benefitted from recent advances in DNA sequencing technologies that provide new or improved diagnostics. However, developing and delivering new treatments for the “genodermatoses” remains challenging. The goal of creating topical preparations that can recover the inherent gene pathology remains largely aspirational. However, recent progress in two fields, the chemistry of topical delivery formulations (lipid nanoparticles) and the molecular biology of gene repair (CRISPR-Cas9, base and prime editing), now presents new opportunities to address that unmet need. In this review, we discuss how lipid nanoparticle delivery vehicles could be used to deliver gene editing tools to formulate topical “gene creams” suitable for the treatment of genodermatoses. We summarise the historical landscape of topical therapeutics and advances in gene editing which may herald an era of new therapies for patients with inherited skin disorders.