Vaults, nanocapsules, and T1D by Gayle Boxx, PhD

Within the cytosol of almost every eukaryotic cell resides a barrel-shaped enigma, the vault nanocapsule. These nanocapsules are 3D nanoprinted by the polyribosome so that each vault contains 78 monomers of the major vault protein (MVP) (https://pubs.acs.org/doi/10.1021/nn504778h#). Since their discovery, researchers have investigated the function and role of vaults in homeostasis, but no clear function has been assigned.

Though almost ubiquitous at the organism or tissue level, vault expression varies widely among different cell types. In the pancreas, for example, MVP messenger RNA is present in exocrine glandular cells and to a lesser extent in the endocrine cells of the islet of Langerhans, yet the MVP protein has only been detected in the exocrine cells. Is it possible that the absence of MVP, or more importantly of vaults, enhances the vulnerability of the cell to external threats? Beta cells, within the islet of Langerhans, are targeted and destroyed in patients with type I diabetes. Would the presence of vaults act to protect these cells or assist in wound healing and repopulation? While this is just a thought experiment, we believe there is a role for vaults in mitigating type I diabetes.

Several natural properties of the vault make it an ideal carrier for therapeutics and vaccines. First, vaults are non-immunogenic. The vault structure is tight, making it difficult for the immune system to gain access necessary to generate a targeted antibody response. Second, vaults are highly conserved, between people and between species. Vaults do not need to be tailored to individual patients to be non-immunogenic and, thus, can be an “off-the-shelf” carrier. Third, vaults are readily taken up by antigen presenting cells and only the payload is acted upon. Antigen payloads are processed, presented and elicit potent B-cell and T-cell responses. Fourth, the structure of the vault suggests it may interact with the nuclear pore. This may be critical for intracellular communication or for delivery of gene therapies.

At Aukera, we have developed a robust portfolio related to the design and manufacture of vault nanocapsules. Our flagship platform, nCap™, is based on the production of recombinant vault nanocapsules in a cell-free synthesis reaction that uses purified components from plants (http://aukerasolutions.com/technology/). nCap™ enables us to package novel molecule payloads during vault assembly, effectively shielding them from the environment during storage and during transport within the body. These vaults are ideal for transporting payloads to antigen presenting cells.  In combination with our other technologies, payload carrying vaults can be directed to specific cell types for a more targeted response. Aukera’s technologies in combination with the natural properties of the vault nanocapsule create a versatile and powerful platform.

Aukera, Inc. is a biotech company that develops and acquires technologies, based on the vault protein nanocapsule. Our goal is to help others develop therapeutics, vaccines and accomplish basic research. Our business model is based on strategic partnerships, out-licensing and custom manufacturing.

Website: http://aukerasolutions.com/

LinkedIn: https://www.linkedin.com/company/aukera-inc./

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