Smart nanomaterials for the delivery of gene editors: beyond LNPs

Abstract

The era of genetic medicine is rapidly unfolding, with major advances in tools for gene editing, silencing, and replacement. Gene editing machinery is versatile and can be delivered in the form of DNA (e.g., plasmids), RNA (e.g., mRNA and guide RNA) or directly in protein form as a ribonucleoprotein complex (RNP). Yet a fundamental challenge shared across these modalities remains: achieving safe, efficient and targeted intracellular delivery. In parallel with progress in the gene correction technologies, smart biomaterials are emerging as powerful platforms capable of overcoming the biological barriers that limit delivery. Lipid nanoparticles (LNPs) have gained remarkable momentum, enabling effective local and systemic administration and driving the first generation of genetic medicines into clinical trials. Beyond LNPs, a diverse landscape of smart materials, including programmable polymers, inorganic nanomaterials, biomimetic vesicles, virus-like particles and hybrid systems, offers complementary advantages for tissue targeting and controlled release. In this review, we summarise recent advances across these material classes, with a focus on design principles that enhance cellular uptake and enable precise intracellular release of gene editing cargos. We highlight applications spanning ex vivo cell engineering to in vivo correction of genetic diseases, and we discuss key translational considerations, including safety, manufacturability, and regulatory expectations. By integrating mechanistic understanding with clinical perspective, this review aims to guide the rational development of next-generation smart materials that will unlock the full therapeutic potential of gene-editing technologies.