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Supermeres are functional extracellular nanoparticles replete with disease biomarkers and therapeutic targets


Zhang QQin , Jeppesen DKDennis K , Higginbotham JNJames N , Graves-Deal RRamona , Trinh VQVincent Q , Ramirez MAMarisol A , Sohn YYoojin , Neininger ACAbigail C , Taneja NNilay , McKinley ETEliot T , Niitsu HHiroaki , Cao ZZheng , Evans RRachel , Glass SESarah E , Ray KCKevin C , Fissell WHWilliam H , Hill SSalisha , Rose KLKristie Lindsey , Huh WJWon Jae , Washington MKMary Kay , Ayers GDGregory Daniel , Burnette DTDylan T , Sharma SShivani , Rome LHLeonard H , Franklin JLJeffrey L , Lee YAYoungmin A , Liu QQi , Coffey RJRobert J . Nature cell biology. 2021 12 9; 23(12). 1240-1254


Extracellular vesicles and exomere nanoparticles are under intense investigation as sources of clinically relevant cargo. Here we report the discovery of a distinct extracellular nanoparticle, termed supermere. Supermeres are morphologically distinct from exomeres and display a markedly greater uptake in vivo compared with small extracellular vesicles and exomeres. The protein and RNA composition of supermeres differs from small extracellular vesicles and exomeres. Supermeres are highly enriched with cargo involved in multiple cancers (glycolytic enzymes, TGFBI, miR-1246, MET, GPC1 and AGO2), Alzheimer’s disease (APP) and cardiovascular disease (ACE2, ACE and PCSK9). The majority of extracellular RNA is associated with supermeres rather than small extracellular vesicles and exomeres. Cancer-derived supermeres increase lactate secretion, transfer cetuximab resistance and decrease hepatic lipids and glycogen in vivo. This study identifies a distinct functional nanoparticle replete with potential circulating biomarkers and therapeutic targets for a host of human diseases.