Coacervation for biomedical applications: innovations involving nucleic acids

Gene therapies, drug delivery systems, vaccines, and many other therapeutics, although seeing breakthroughs over the past few decades, still suffer from poor stability, biocompatibility, and targeting. Coacervation, a liquid-liquid phase separation phenomenon, is a pivotal technique increasingly employed to enhance the effectiveness of therapeutics. Through coacervation strategies, many current challenges in therapeutic formulations can be addressed due to the tunable nature of this technique. However, much remains to be explored to enhance these strategies further and scale them from the benchtop to industrial applications. In this review, we highlight the underlying mechanisms of coacervation, elucidating how factors such as pH, ionic strength, temperature, chirality, and charge patterning influence the formation of coacervates and the encapsulation of active ingredients. We then present a perspective on current strategies harnessing these systems, specifically for nucleic acid-based therapeutics. These include peptide-, protein-, and polymer-based approaches, nanocarriers, and hybrid methods, each offering unique advantages and challenges. Nucleic acid-based therapeutics are crucial for designing rapid responses to diseases, particularly in pandemics. While these exciting systems offer many advantages, they also present limitations and challenges which are explored in this work. Exploring coacervation in the biomedical frontier opens new avenues for innovative nucleic acid-based treatments, marking a significant stride towards advanced therapeutic solutions.