Abstract <p>The biomedical research of nucleic acids as therapeutics and their medical applications has been steadily progressing. Identifying the fundamental regulatory roles of nucleic acids and their potential use in the medical field is of major pursuit in current and future research endeavors. Research into nucleic acids for the treatment of vascular diseases has been an emerging avenue as nucleic acids have the ability to treat a variety of pathologies including atherosclerosis. A large part of the translational research in relation to nucleic acids is the development and optimization of drug delivery technologies that can harness the full potential of these molecules, providing untapped, novel therapeutic agents. Specifically, the use of biomaterial delivery systems, consisting of polymers, lipids, and inorganic materials, allows for the protection of nucleic acid therapeutics to promote targeting to regions of vascular damage. While the relevance of nucleic acid therapeutics has been well documented, their functionality for diseases affecting the peripheral vasculature, and the need for biomaterials systems capable of improving their efficacy, has been lacking. This review aims to provide an overview of the biomaterial technologies tested for nucleic acid delivery, relative to the science of applied vascular tissue engineering.</p> Lay Summary <p>The study of nucleic acids as therapeutic agents is rapidly advancing, with significant potential for treating diseases. These molecules play key roles in regulating biological processes and can be engineered for medical applications. One exciting area of research focuses on using nucleic acids to treat vascular diseases, such as atherosclerosis. To maximize their therapeutic impact, researchers are developing innovative delivery systems made from materials like polymers, lipids, and inorganic substances. These biomaterial-based carriers protect nucleic acids and target damaged blood vessels more effectively. This review highlights the latest biomaterial technologies in nucleic acid delivery and their role in vascular tissue repair. Future research will focus on refining biomaterial delivery systems to enhance the stability, targeting precision, and therapeutic efficacy of nucleic acid-based treatments. Efforts will also include exploring emerging materials, such as hybrid composites, and integrating advanced bioengineering approaches to address vascular diseases and other challenging medical conditions.</p> Graphical Abstract <p></p>