Extracellular vesicles (EVs) are produced by all cells in the body. These biological nanoparticles facilitate cellular communication through the transport of diverse cargoes, including small molecules, proteins, and nucleic acids. mRNA cargoes have gained particular interest given their role in the translation of functional proteins. As a biomarker platform, EVs can be found in nearly all biofluids-blood, mucus, urine, cerebrospinal fluid, and saliva-providing real-time insight into parent cell and tissue function. mRNAs carried by EVs are protected from degradation, resulting in improved detection compared to free mRNA, and recent work demonstrates promising results in using these mRNA cargoes as biomarkers for cancer, neurological diseases, infectious diseases, and gynecologic and obstetric outcomes. Furthermore, given the innate cargo carrying, targeting, and barrier crossing abilities of EVs, these structures have been proposed as therapeutic carriers of mRNA. Recent advances demonstrate methods for loading mRNAs into EVs for a range of disease indications. Here, we review recent studies using EVs and their mRNA cargoes as diagnostics and therapeutics. We discuss challenges associated with EVs in diagnostic and therapeutic applications and highlight opportunities for future development.
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http://dx.doi.org/10.7150/thno.93115 | DOI Listing |
Function (Oxf)
January 2025
Department of Health and Exercise Science, College of Health and Human Sciences, Colorado State University, Fort Collins, CO, USA.
Extracellular vesicles (EVs) are functional lipid-bound nanoparticles trafficked between cells and found in every biofluid. It is widely claimed that EVs can be secreted by every cell, but the quantity and composition of these EVs can differ greatly among cell types and tissues. Defining this heterogeneity has broad implications for EV-based communication in health and disease.
View Article and Find Full Text PDFVaccines (Basel)
January 2025
Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, School of Medicine, University of California Irvine, Irvine, CA 92697, USA.
Background: Nucleoside-modified mRNA encapsulated in lipid nanoparticles (LNPs) have emerged as a promising vaccine strategy, especially for COVID-19. While the LNPs protect mRNA from degradation and efficiently deliver the mRNA to antigen-presenting cells, the effect of lipid composition on the immunogenicity and protective efficacy of mRNA/LNP vaccines is not well characterized. Studies on using the mRNA/LNP platform for vaccines have largely focused on the nucleic acid cargo with less attention paid to the LNP vehicle.
View Article and Find Full Text PDFBiomaterials
January 2025
Institute of Health Innovation & Technology, National University of Singapore, Singapore, 117599, Singapore; Department of Biomedical Engineering, National University of Singapore, Singapore, 117576, Singapore; NUS Tissue Engineering Program, National University of Singapore, Singapore, 117510, Singapore. Electronic address:
Transfection of proteins, mRNA, and chimeric antigen receptor (CAR) transgenes into immune cells remains a critical bottleneck in cell manufacturing. Current methods, such as viruses and bulk electroporation, are hampered by low transfection efficiency, unintended transgene integration, and significant cell perturbation. The Nanostraw Electro-actuated Transfection (NExT) technology offers a solution by using high aspect-ratio nanostraws and localized electric fields to precisely deliver biomolecules into cells with minimal disruption.
View Article and Find Full Text PDFStem Cell Rev Rep
January 2025
Department of Internal Medicine, Reproduction and Population Health, Faculty of Veterinary Medicine, University of Ghent, Salisburylaan 133, Merelbeke, B-9820, Belgium.
Over the past decade, research on embryo-derived extracellular vesicles (EVs) has unveiled their critical roles in embryonic development and intercellular communication. EVs secreted by embryos are nanoscale lipid bilayer vesicles that carry bioactive cargo, including proteins, lipids, RNAs, and DNAs, reflecting the physiological state of the source cells. These vesicles facilitate paracrine and autocrine signaling, influencing key processes such as cell differentiation, embryo viability, and endometrial receptivity.
View Article and Find Full Text PDFBiomater Sci
January 2025
Department of Bio and Brain Engineering, and KAIST Institute for Health Science and Technology, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.
Incorporation of polyethylene glycol (PEG) is widely used in lipid nanoparticle (LNP) formulation in order to achieve adequate stability due to its stealth properties. However, studies have detected the presence of anti-PEG neutralizing antibodies after PEGylated LNP treatment, which are associated with anaphylaxis, accelerated LNP clearance and premature release of cargo. Here, we report the development of LNPs incorporating ganglioside, a naturally occurring stealth lipid, as a PEG-free alternative.
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