Bioactive Extracellular Nanovesicles
The living cells of animals, plants and micro-organisms including bacteria and fungi produce extracellular vesicles (EVs) such as microvesicles, exosomes and exomeres through endosomal pathways and derived from the plasma membrane. During EV biogenesis, cells selectively assemble lipid, protein and nucleic acid contents within the nascent nanovesicles. The bioactivity of EVs depends on their protein and nucleic acid contents. The lipid content constitutes the bilayer membrane that protects protein and RNA molecules from degradation in transit and facilitates biodistribution across tissue barriers such as the blood-brain barrier and into
solid tissue masses like tumors. The specific lipid, protein and nucleic acid content of EVs depends on the parent cell type and tissue environment, which correspondingly defines their biological effects. Localization to specific tissues and endocytosis of EVs by specific cell types is determined in part by the composition of the EV membrane and its associated proteins. Each of these intrinsic biological characteristics of EVs can be further developed into enhanced cellular targeting and bioactivity in drug development. Analytical methods that precisely identify EV contents can also provide the framework for more sensitive and accurate diagnostic tests.
With a focus on advancements in medical diagnostics and therapeutics through EV research and development, EV Biologics is building a world-class team of molecular biologists, analytical biochemists, nanoparticle biophysicists, synthetic organic chemists biomedical engineers, software and systems engineers, as well as physicians and surgeons specializing in regenerative medical technology. The motivation of our team to push back the frontiers of EV biotechnology stems from their own personal and professional experience with health and disease and the promise of next-generation solutions based on stem cell and EV therapy.
The biological molecules that make up EVs are primarily lipids, proteins and nucleic acids. Different types of phospholipids are involved with the biogenesis of EVs and can be indicative of the state of their parent cells. EV proteins include signaling cytokines, receptors, enzymes, binding proteins and membrane proteins. Bioactive nucleic acids in EVs are in large part RNA molecules, which may comprise coding and non-coding RNA. Each of these biomolecules contributes to the biological activity of EVs.
As lipid nanoparticles, EVs have the capacity to distribute throughout the circulation, across membrane barriers and into solid tissues due to their small size and lipid membrane. This ability means that EVs have the potential to reach cellular targets that are much more difficult to reach with small molecule drugs. There is a tendency for EVs to accumulate in certain organs and tissues, which plays a role in their natural bioactivity. Modification of membrane proteins and other biological moieties can further refine their cellular targeting.
After target cells internalize EVs, their proteins and nucleic acids interact with cellular biochemical mechanisms and have the capacity to alter cell behavior. EV proteins can directly influence cellular signaling cascades and enzymatic pathways. RNA, both coding and non-coding, has the ability to influence cellular activity through direct transcription of mRNA or miRNA interference in endogenous protein production, respectively. Overexpression of specific proteins and RNA by design can create desired therapeutic effects.