Current challenges and future directions for engineering extracellular vesicles for heart, lung, blood and sleep diseases

Abstract

Extracellular vesicles (EVs) carry diverse bioactive components including nucleicacids, proteins, lipids and metabolites that play versatile roles in intercellular andinterorgan communication. The capability to modulate their stability, tissue-specifictargeting and cargo render EVs as promising nanotherapeutics for treating heart,lung, blood and sleep (HLBS) diseases. However, current limitations in large-scalemanufacturing of therapeutic-grade EVs, and knowledge gaps in EV biogenesis andheterogeneity pose significant challenges in their clinical application as diagnosticsor therapeutics for HLBS diseases. To address these challenges, a strategic workshopwith multidisciplinary experts in EV biology and U.S. Food and Drug Administration(USFDA) officials was convened by the National Heart, Lung and Blood Institute. Thepresentations and discussions were focused on summarizing the current state of sci-ence and technology for engineering therapeutic EVs for HLBS diseases, identifyingcritical knowledge gaps and regulatory challenges and suggesting potential solutionsto promulgate translation of therapeutic EVs to the clinic. Benchmarks to meet thecritical quality attributes set by the USFDA for other cell-based therapeutics werediscussed. Development of novel strategies and approaches for scaling-up EV pro-duction and the quality control/quality analysis (QC/QA) of EV-based therapeuticswere recognized as the necessary milestones for future investigations.