Endosomal Escape Enhancing Compounds Facilitate Functional Delivery of Extracellular Vesicle Cargo
2019; Future Medicine; Volume: 14; Issue: 21 Linguagem: Inglês
10.2217/nnm-2019-0061
ISSN1748-6963
AutoresNikki Heath, Xabier Osteikoetxea, Taiana Mia de Oliveria, Elisa Lázaro‐Ibáñez, Olga Shatnyeva, Christina Schindler, Natalie J. Tigue, Lorenz M. Mayr, Niek Dekker, R. Overman, Rick Davies,
Tópico(s)RNA Interference and Gene Delivery
ResumoAim: Extracellular vesicles (EVs) are desirable delivery vehicles for therapeutic cargoes. We aimed to load EVs with Cre recombinase protein and determine whether functional delivery to cells could be improved by using endosomal escape enhancing compounds. Materials & methods: Overexpressed CreFRB protein was actively loaded into EVs by rapalog-induced dimerization to CD81FKBP, or passively loaded by overexpression in the absence of rapalog. Functional delivery of CreFRB was analysed using a HEK293 Cre reporter cell line in the absence and presence of endosomal escape enhancing compounds. Results: The EVs loaded with CreFRB by both active and passive mechanisms were able to deliver functional CreFRB to recipient cells only in the presence of endosomal escape enhancing compounds chloroquine and UNC10217938A. Conclusion: The use of endosomal escape enhancing compounds in conjunction with EVs loaded with therapeutic cargoes may improve efficacy of future EV based therapeutics.
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