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Intracellular molecular targets of luminal payloads delivered by engineered MSC-sEVs refers to the diverse array of biological molecules—such as messenger RNAs, transcription factors, and signaling kinases—that are modulated by therapeutic agents encapsulated within Mesenchymal Stem Cell-derived small Extracellular Vesicles (MSC-sEVs) (Kalluri & LeBleu, 2020). MSC-sEVs are natural, lipid-bilayered nanoparticles that can be bioengineered to carry specific luminal payloads, including microRNAs (miRNAs), small interfering RNAs (siRNAs), or recombinant proteins, to recipient cells (O'Brien et al., 2020). Upon internalization via endocytosis or membrane fusion, these payloads are released into the cytoplasm where they interact with their respective targets to alter cellular behavior, such as silencing oncogenes in cancer or activating regenerative pathways in damaged tissues (Wiklander et al., 2015). Because this term describes a delivery platform rather than a single discrete molecule, the specific targets are highly variable and depend entirely on the payload selected for a particular therapeutic application. This approach leverages the innate homing abilities and low immunogenicity of MSC-derived vesicles to achieve precise, intracellular drug delivery (Yin et al., 2019). Common examples include the delivery of miR-146a to target IRAK1 in inflammatory diseases or the delivery of siRNA to target KRAS in pancreatic cancer.
Engineered MSC-sEVs facilitate the intracellular delivery of therapeutic payloads (e.g., RNAi, proteins) which then bind to and modulate specific molecular targets such as mRNA or signaling proteins (Kalluri & LeBleu, 2020).
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