Section of Rheumatology, Allergy and Clinical Immunology, Department of Internal Medicine, School of Medicine, Yale University, 217 TAC Building South, 333 Cedar Street, New Haven, CT 06520, USA.
Int J Mol Sci. 2022 May 31;23(11):6192. doi: 10.3390/ijms23116192.
Carrier effects of extracellular vesicles (EV) like exosomes refer to properties of the vesicles that contribute to the transferred biologic effects of their contents to targeted cells. This can pertain to ingested small amounts of xenogeneic plant miRNAs and oral administration of immunosuppressive exosomes. The exosomes contribute carrier effects on transfers of miRNAs by contributing both to the delivery and the subsequent functional intracellular outcomes. This is in contrast to current quantitative canonical rules that dictate just the minimum copies of a miRNA for functional effects, and thus successful transfers, independent of the EV carrier effects. Thus, we argue here that transfers by non-canonical minute quantities of miRNAs must consider the EV carrier effects of functional low levels of exosome transferred miRNA that may not fit conventional reductionist stoichiometric concepts. Accordingly, we have examined traditional stoichiometry vs. systems biology that may be more appropriate for delivered exosome functional responses. Exosome carrier properties discussed include; their required surface activating interactions with targeted cells, potential alternate targets beyond mRNAs, like reaching a threshold, three dimensional aspects of the RNAs, added EV kinetic dynamic aspects making transfers four dimensional, and unique intracellular release from EV that resist intracellular digestion in phagolysosomes. Together these EV carrier considerations might allow systems analysis. This can then result in a more appropriate understanding of transferred exosome carrier-assisted functional transfers. A plea is made that the miRNA expert community, in collaboration with exosome experts, perform new experiments on molecular and quantitative miRNA functional effects in systems that include EVs, like variation in EV type and surface constituents, delivery, dose and time to hopefully create more appropriate and truly current canonical concepts of the consequent miRNA functional transfers by EVs like exosomes.
细胞外囊泡（EV），如外泌体的载体效应是指囊泡的特性，有助于其内容物向靶细胞传递生物效应。这可能涉及摄入少量异种植物 miRNA 和口服免疫抑制性外泌体。外泌体通过促进 miRNA 的传递和随后的细胞内功能结果，对 miRNA 的传递产生载体效应。这与当前定量的规范规则形成对比，规范规则只规定了 miRNA 发挥功能作用的最小拷贝数，因此与 EV 载体效应无关，转移是成功的。因此，我们在这里认为，非规范的 miRNA 微量转移必须考虑 EV 载体效应，即功能性低水平外泌体转移 miRNA 的效应，而这些效应可能不符合传统的还原论计量概念。因此，我们研究了传统的计量学与系统生物学，后者可能更适合于研究外泌体的功能反应。讨论的外泌体载体特性包括：它们与靶细胞所需的表面激活相互作用、超越 mRNAs 的潜在替代靶标，如达到阈值、RNA 的三维方面、添加的 EV 动力学动态方面使转移成为四维的，以及从 EV 中独特的细胞内释放，防止在吞噬溶酶体中被细胞内消化。这些 EV 载体的考虑因素可能允许系统分析。这可以更准确地理解转移的外泌体载体辅助功能转移。我们呼吁 miRNA 专家社区与外泌体专家合作，在包括 EV 在内的系统中进行新的分子和定量 miRNA 功能效应实验，如 EV 类型和表面成分、传递、剂量和时间的变化，希望能创造出更合适和真正符合当前规范概念的 EV，如外泌体，对 miRNA 功能转移的理解。
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