The evolving paradigm of extracellular vesicles in intercellular signaling and delivery of therapeutic RNAs
Year: 2022
Type: article
Abstract: Extracellular vesicles (EVs) are approximately 30- to 150-nM particles that are generated by cells and are thought to mediate the transfer of bioactive cargo. 1 Witwer K.W. Wolfram J. Extracellular vesicles versus synthetic nanoparticles for drug delivery. Nat. Rev. Mater. 2021; 6: 103-106https://doi.org/10.1038/s41578-020-00277-6 Crossref Scopus (98) Google Scholar Substantial evidence suggests that an under-appreciated role of EVs is the mediation of intercellular signaling via microRNAs (miRNAs). 1 Witwer K.W. Wolfram J. Extracellular vesicles versus synthetic nanoparticles for drug delivery. Nat. Rev. Mater. 2021; 6: 103-106https://doi.org/10.1038/s41578-020-00277-6 Crossref Scopus (98) Google Scholar ,2 Kojima R. Bojar D. Rizzi G. Hamri G.C. El-Baba M.D. Saxena P. Auslander S. Tan K.R. Fussenegger M. Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson's disease treatment. Nat. Commun. 2018; 9: 1305https://doi.org/10.1038/s41467-018-03733-8 Crossref PubMed Scopus (336) Google Scholar However, the concept that miRNAs packaged into EVs mediate intercellular signaling has recently been called into question by Albanese and Chen et al., 3 Albanese M. Chen Y.F.A. Huls C. Gartner K. Tagawa T. Mejias-Perez E. Keppler O.T. Gobel C. Zeidler R. Shein M. et al. MicroRNAs are minor constituents of extracellular vesicles that are rarely delivered to target cells. PLoS Genet. 2021; 17: e1009951https://doi.org/10.1371/journal.pgen.1009951 Crossref PubMed Scopus (67) Google Scholar who report that miRNAs do not seem to be packaged appreciably into EVs and, furthermore, when they are, they have little to no effect on recipient cells. These observations call into question myriad publications over the last decade that suggested that EV-packaged miRNAs alter target cell function and play a role in disease development and even, for example, in reprogramming of cells toward an oncogenic phenotype. 2 Kojima R. Bojar D. Rizzi G. Hamri G.C. El-Baba M.D. Saxena P. Auslander S. Tan K.R. Fussenegger M. Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson's disease treatment. Nat. Commun. 2018; 9: 1305https://doi.org/10.1038/s41467-018-03733-8 Crossref PubMed Scopus (336) Google Scholar ,4 Ye Y. Zhang X. Xie F. Xu B. Xie P. Yang T. Shi Q. Zhang C.Y. Zhang Y. Chen J. et al. An engineered exosome for delivering sgRNA:Cas9 ribonucleoprotein complex and genome editing in recipient cells. Biomater. Sci. 2020; 8: 2966-2976https://doi.org/10.1039/d0bm00427h Crossref PubMed Scopus (65) Google Scholar
Source: Molecular Therapy
Authors: Kevin V. Morris, Kenneth W. Witwer
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,900
Awards: G1045126187, G168982208, G2965151290, Novel Separation Methods for exRNA Carriers: Extracellular Vesicles, Lipoprotein Particles, and Protein Aggregates, Next-generation extracellular vesicle biologics to target central nervous system and peripheral reservoirs of HIV, Extracellular Vesicle and Extracellular RNA Biomarkers of HIV-1 Central Nervous System Pathogenesis and Cigarette Use
OpenAlex ID: W4281708218