Chronic Kidney Disease

At lab meeting today, a collaborator presented her work to us. She is working on treatments for chronic kidney disease. Before using our lab's vaults, she showed that this RGD-peptide (just a small, 4 amino-acid protein) could help reduce damaging fibronectin growth in the kidney, alleviating some of the tissue damage of chronic kidney disease. And then she made a new vault with the RGD-peptide encapsulated. The vault can open and close, and since everything in the blood passes through the kidney, the vaults will no doubt encounter the Integrin receptor, which is the target receptor for the RGD-peptide. Integrin receptor is a receptor found going from inside the cell to far outside, and it is one way for the cell to attach itself to other things, such as extracellular matrix compounds, mainly fibronectin. So the vault encapsulated RGD-peptide makes its way to the kidney cells, where things get exchanged between blood cell and kidney cell. And the vault "breathes" and opens up to release the RGD-peptide, which finds itself near the Integrin receptor, competing with fibronectin to bind. So RGD-peptide binds to Integrin, ousting fibronectin. Therefore, you reduce the amount of fibronectin stuck on the kidney cells and reduce the amount of tissue damage as a consequence of it. She also did mice studies where they treated mice that had chronic kidney disease with varying amounts of the RGD-peptide, and showed improvements in renal tissue damage.

Woohoo Vaults as a drug delivery vehicle!

YEah I might as well talk about that a little.

So one of the problems in medicine is drug delivery vehicles. How can you find a drug delivery vehicle that satisfies these requirements?

1. doesn't cause an immune response
2. will be taken up by cells
3. can protect the drug
4. can be targeted to specific cells

Since vaults are endogenous and not a synthetic nanocapsule, they instantly fit the most difficult for synthetic kinds: #1, making them an easy choice for drug delivery. They consist of two half-barrels, which can open and close. The half-barrels themselves are sort of cut up into petals that they think can open and close. There is some good evidence for the two half-barrels opening and closing (breathing, yes, we melodramatic scientists).