Microneedle systems for delivering nucleic acid drugs

Background Nucleic acid-based gene therapy is a promising technology that has been used in various applications such as novel vaccination platforms for infectious/cancer diseases and cellular reprogramming because of its fast, specific, and effective properties. Despite its potential, the parenteral nucleic acid drug formulation exhibits instability and low efficacy due to various barriers, such as stability concerns related to its liquid state formulation, skin barriers, and endogenous nuclease degradation. As promising alternatives, many attempts have been made to perform nucleic acid delivery using a microneedle system. With its minimal invasiveness, microneedle can deliver nucleic acid drugs with enhanced efficacy and improved stability. Area covered This review describes nucleic acid medicines' current state and features and their delivery systems utilizing non-viral vectors and physical delivery systems. In addition, different types of microneedle delivery systems and their properties are briefly reviewed. Furthermore, recent advances of microneedle-based nucleic acid drugs, including featured vaccination applications, are described. Expert opinion Nucleic acid drugs have shown significant potential beyond the limitation of conventional small molecules, and the current COVID-19 pandemic highlights the importance of nucleic acid therapies as a novel vaccination platform. Microneedle-mediated nucleic acid drug delivery is a potential platform for less invasive nucleic acid drug delivery. Microneedle system can show enhanced efficacy, stability, and improved patient convenience through self-administration with less pain.