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for delivery of plasmid DNA and mRNA transform biology and medicine, offering powerful tools for gene therapy, vaccine development, cancer immunotherapy, and regenerative medicine. Plasmid DNA provides a relatively stable and sustained expression of the genes which also provides the basic groundwork for long-lasting therapeutic. At the same time, mRNA has also demonstrated more appropriateness for dynamic and time-sensitive applications due to its short-lived and accurate translation capabilities, such as during the development of mRNA-based COVID-19 vaccines. Despite their unique advantages, however, the efficient delivery of these biomolecules poses challenges including immune system activation, enzymatic degradation, and limited cellular uptake. The structural and functional features of plasmid DNA and mRNA highlighted the positive functions that underpin their complementary roles in next-generation biomedical applications. In addition, it highlights the novel delivery routes across lipid nanoparticles, polymeric systems, biomimetic carriers, and hybrid applied sciences which can resolve long-standing challenges to efficient distribution. Emerging technologies such as CRISPR gene editing, self-amplifying RNA, and multiplexed nanoparticles are also increasing the utility of these systems. Significant advances in the delivery of plasmid DNA and mRNA molecules have revolutionized vaccine development, opened new avenues in personalized medicine, and have also inspired a future with engineerable tissues. As these innovations develop, they are predicted to go beyond current limitations and bring around a fresh era of accurate medication taking on one of the global healthcare's most complex challenges. Our revolutionary delivery methods provide stability and simplicity, transforming medical advances.
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http://dx.doi.org/10.1016/bs.ai.2024.12.001 | DOI Listing |
Microbiol Spectr
September 2025
Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
Efficient DNA delivery is essential for genetic manipulation of mycobacteria and for dissecting their physiology, pathogenesis, and drug resistance. Although electroporation enables transformation efficiencies exceeding 10⁵ CFU per µg DNA in and , it remains highly inefficient in many nontuberculous mycobacteria (NTM), including . Here, we discovered that NTM such as exhibit exceptional tolerance to ultra-high electric field strengths and that hypertonic preconditioning partially protects cells from electroporation-induced damage.
View Article and Find Full Text PDFNAR Cancer
September 2025
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States.
The mycotoxin, aflatoxin B (AFB), is a potent mutagen that contaminates agricultural food supplies. After ingestion, AFB is oxidized into a reactive electrophile that alkylates DNA, forming bulky lesions such as the genotoxic formamidopyrimidine lesion, AFB-Fapy dG. This lesion is mainly repaired by nucleotide excision repair (NER) in bacteria; however, in humans the picture is less clear.
View Article and Find Full Text PDFInt J Biol Macromol
September 2025
CNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, 3004-504, Portugal; CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, 3004-504, Portugal; Faculty of Pharmacy, University of Coimbra, Coimbra, 3000-548, Portugal. Electronic a
The increasing prevalence of respiratory disorders highlights the urgent need for effective mucosal vaccines that elicit targeted immune responses at pathogen entry sites. However, the advancement of mucosal vaccines is limited by challenges in antigen delivery and overcoming mucosal immune tolerance. In this study, we developed a gene delivery platform using chitosan functionalized with lactobionic acid (LA) to enhance targeting of antigen-presenting cells and to form stable DNA polyplexes with high transfection efficiency.
View Article and Find Full Text PDFAutoimmunity
December 2025
Medicinal Genomics, Beverly, MA, USA.
For some of the COVID-19 vaccines, the drug substances released to market were manufactured differently than those used in clinical trials. Manufacturing nucleoside-modified mRNA (modRNA) for commercial COVID-19 vaccines relies on RNA polymerase transcription of a plasmid DNA template. Previous studies identified high levels of plasmid DNA in vials of modRNA vaccines, suggesting that the removal of residual DNA template is problematic.
View Article and Find Full Text PDFStructure
September 2025
Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Mohali, SAS Nagar (Mohali), Punjab, India. Electronic address:
The structural maintenance of chromosomes (SMC)-family Wadjet complex restricts plasmid transformation in bacteria through a distinctive mechanism coupling DNA loop extrusion and cleavage. In this issue of Structure, Roisné-Hamelin et al. report the biochemical reconstitution and structure of a type II Wadjet complex, revealing a shared overall mechanism and notable architectural differences compared to related type I complexes.
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