en Immune responses, deficiencies and vaccine candidates Immune responses, deficiencies and vaccine candidates Review article Review article <span style="font-size:10.0pt"><span style="line-height:107%"><span new="" roman="" style="font-family:" times=""><span style="color:black">The rapid development of nucleic acid-based vaccines represents a major advancement in immunization strategies, characterized by their reliance on host cellular machinery to produce antigens.<b> </b>These third-generation platforms, including DNA and mRNA vaccines, offer key advantages such as rapid scalability, simplified manufacturing, and versatility in targeting a broad spectrum of </span></span></span></span><span style="font-size:10.0pt"><span style="line-height:107%"><span new="" roman="" style="font-family:" times="">diseases caused by infectious pathogens or conditions like cancer. <span style="color:black">While they avoid the use of live pathogens and </span>thereby minimize many infection-related risks associated with pathogen reversion, potential side effects such as immune overactivation or off-target responses remain key safety considerations. <span style="color:black">Nanotechnology, particularly lipid nanoparticle (LNP) systems, has emerged as a critical enabler in addressing these limitations. LNPs enhance nucleic acid stability, promote cellular uptake, and facilitate targeted delivery, thereby improving both immune activation and overall safety profiles. Innovations in ionizable lipid design, PEGylation, and size-controlled formulations have been pivotal to the success of mRNA vaccines </span>in response to <span style="color:black">the COVID-19 pandemic. This review focuses primarily on LNPs as delivery platforms, while also discussing emerging nanotechnologies under investigation in both preclinical and clinical settings. By examining advances in nanoparticle engineering, delivery strategies, and disease-specific applications, this review aims to provide a comprehensive overview of how nanotechnology is reshaping the future of nucleic acid vaccine development. </span>This <span style="color:black">underscores the transformative potential of nanoscale delivery systems in overcoming current barriers and accelerating the innovation of next-generation vaccines.</span></span></span></span> Nucleic acid vaccines, Lipid nanoparticles (LNPs), Vaccine stability, Vaccine delivery, Adjuvants, mRNA vaccines, Nanotechnology 88 96 http://jommid.pasteur.ac.ir/browse.php?a_code=A-10-441-6&slc_lang=en&sid=1 Sohameh Mohebbi s.mohebbi@aletaha.ac.ir 0000-0002-4512-175X No Department of Biology, Faculty of Basic Science, Ale Taha Institute of Higher Education, Tehran, Iran Maryam Ghanbari Ghanbari.tmu@gmail.com 0000-0002-7183-3769 Yes Department of Microbial Biotechnology, Faculty of Biological Science, Tehran North Branch, Islamic Azad University, Tehran, Iran Kazem Baesi kbaesi@gmail.com 0000-0001-5483-0008 No Hepatitis and AIDS Department, Pasteur Institute of Iran, Tehran, Iran