AGS' science and technology stand on the shoulders of a giant : the MEVs.
MEVs are natural nanoparticles known as extracellular vesicles from microalgae, produced by Chlorella. Chlorella is a living fossil having existed on Earth for 2-3 billion years, long before the emergence (and disappearance) of most living organisms, such as plants and animals, that have existed since those ancient times.
Chlorella is an ancestor of the entire living world around us. Chlorella cells proliferated in the warm oceans of a Precambrian planet, where rocky continents were covered by volcanic eruptions, the atmosphere was sulphur-yellow and acidic, and gaseous oxygen was absent. Animals and plants, as we know them today or as recorded in paleontological registers, did not yet exist. Most green plants today are derived, in some way, from microalgae such as Chlorella.
Chlorella is a unicellular, autotrophic, haploid microalgae that thrives in mild freshwater environments across the globe. Chlorella cells are natural producers of large quantities of functional MEVs.
Chlorella biomass has been consumed as a food supplement worldwide for many decades. Numerous reports link the regular consumption of Chlorella biomass with improved well-being, protection against various systemic diseases, and enhanced health of the skin and mucous membranes.
Chlorella vulgaris has been recognized as safe by the FDA (GRAS certificate).
AGS has pioneered the discovery that MEVs can be an unparalleled delivery system and develops them as a potent universal tool for the delivery of therapeutics, vaccines and gene therapies.
MEVs such as other EVs are cell-derived lipid-bilayer vesicles that carry bioactive molecules; they are secreted to the extracellular environment and deliver their payload to surrounding recipient cells modulating the physiological conditions of those recipient cells.
Compared to alternative delivery systems, MEVs exhibit astonishing properties. They lack most, if not all, of the canonical and aeons later-developed surface markers found in living mammalian or plant EVs. They are non-toxic, do not elicit a neutralizing immune response in mammals, and possess the ability to traverse stringent biological barriers within the mammalian body.
Additionally, MEVs can be exo-loaded and accommodate a variety of biologically active molecules (mRNAs, siRNAs, peptides, proteins, oligos, plasmids, etc.). Loaded MEVs protect and transport their payloads and deliver them to the appropriate cellular compartments of the recipient cells, for proper expression and processing.
MEVs can travel via axonal transport and cross over synapses. MEVs move through the choroid to reach retinal cells. MEVs withstand the acidic environment of the stomach and go through the intestine; finally, MEVs find their way to activate TLR receptors buried inside cell endosomes.
MEVs (microalgal extracellular vesicles) are the cornerstone of the AGS technology platform, forming the basis for our therapeutic, vaccinal, and gene therapy products.
MEVs are naturally occurring, nanosized lipid-bilayer particles known as extracellular vesicles, derived from unicellular green microalgae like Chlorella. These MEVs are a potent tool, honed by over two billion years of natural evolution, originating from an era predating the existence of plants or animals.
MEVs have evolved to perform a fundamental role: conveying biologically and genetically significant messages between cells. This involves encapsulating relevant molecules, transporting them through and protecting them from harsh extracellular environments, and delivering their payloads to recipient target cells.
AGS has pioneered the discovery that MEVs can be an unparalleled delivery system and develops them as a potent universal tool for the delivery of therapeutics, vaccines and gene therapies.
As a delivery tool for biological and genetic modalities, MEVs meet all the criteria for an optimal delivery system. They are biologically compatible, non-toxic, non-immunogenic, and exhibit ideal biodistribution, tissue/cell tropism, and clearance. MEVs offer highly efficient loading capabilities, versatility for various bioactive payloads (small and large), and protection of these payloads from degradation by either biological fluids or environmental agents. They can overcome stringent biological barriers and deliver their cargo efficiently to target cells and specific cell compartments, including the cytoplasm, the nucleus, the phagosomes, and the TLR-based endosomes, among others. Furthermore, MEVs are produced at high yields and manufactured cost-effectively.
Additionally, MEVs offer advantages beyond those required for delivery systems. MEV production is a green and sustainable process, not necessitating complex culture media, toxic solvents, or human cells.
AGS operates a comprehensive suite of technologies to develop its proprietary therapeutic, vaccinal, and gene therapy candidates. These include:
(1)
Cultivating microalgae cells under highly controlled conditions.
(11)
Harvesting microalgae cells to consistently produce and release large quantities of naïve MEVs.
(111)
Purifying the naïve MEVs.
(1v)
Designing the desired payload based on internal research and public knowledge.
(v)
Loading purified MEVs with the payload to create loaded MEVs.
(v1)
Fully characterizing the loaded MEVs.
(v11)
Evaluating the biological activity and therapeutic efficacy of the payload through MEV-mediated delivery in suitable in vitro cell models and in vivo animal models relevant to the disease of interest.
(v111)
Conducting preclinical and clinical evaluations of MEV-based candidate products loaded with therapeutic payloads.
2024. Microalgae Extracellular Vesicle Based Gene Therapy Vectors (MEV-GTVs), Their Preparation, and Uses Thereof. Drittanti et al.
2024. Ocular Delivery of Active Agents via Microalgae Extracellular Vesicles. Drittanti et al.
2023. Extracellular Vesicles From Microalgae, Their Use for Vaccines and for Immunomodulation. Drittanti et al.
2022. Extracellular Vesicles from Microalgae, Their Biodistribution Upon Intranasal Administration, and Uses. Drittanti et al.
2022. Extracellular Vesicles from Microalgae, Their Biodistribution Upon Administration, and Uses. Drittanti et al.
2022. Extracellular Vesicles from Genetically Modified Microalgae Containing Endogenously Loaded Cargo, Their Preparation, and Uses. Drittanti et al.
2021. Extracellular Vesicles from Microalgae, their Preparation, and Uses. Drittanti et al.
2020. Chlorella-Based Production of Extracellular Vesicle-Embedded Small RNAs for Prophylactic or Therapeutic Applications. Navarro et al. Exclusive license from CNRS to AGS Therapeutics.
AGS is proactive in safeguarding its scientific discoveries and novel ideas through patents.
Since its inception, AGS has developed a robust and continually expanding portfolio of interconnected patents. These patents establish AGS as a leader in the field of microalgae extracellular vesicles (MEVs) within the healthcare sector and beyond.
Our patent portfolio not only safeguards our current technology platforms and product pipeline but also extends significantly beyond that, to protect various verticals (ophthalmology, inflammatory diseases, respiratory diseases, intestinal disorders, brain and CNS disorders, dermatology/skin care, vaccines, and gene therapy) where we have initiated pioneering work. See the list of filed patents below.
AGS' inventions are abundant with innovative ideas and groundbreaking discoveries. This is attributed to the unique, unexpected, and outstanding characteristics of MEVs, which distinguish them from other delivery systems, including mammalian extracellular vesicles or exosomes (EVs), lipid nanoparticles (LNPs), and adeno-associated viral vectors (AAV vectors).
Chlorella, a living fossil existing on Earth for approximately 2.5 billion years, has preceded the emergence of all other forms of plants and animals, both living and extinct. This anteriority and longevity is likely a significant reason why the behavior, properties, and applications of MEVs are non-obvious and cannot be predicted based on other delivery systems.
