Difference between revisions of "Part:BBa K4586000"

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cyclic citrullinated peptide (CCP1)

Part Description

This part codes for cyclic citrullinated vimentin which is a synthetic peptide designed to detect and measure specific antibodies that are elevated in autoimmune diseases, especially rheumatoid arthritis.

Usage

This part is implicated within our design in two units: first, the external domain (sensor) of our SYNNOTCH receptor that binds to the BCR of autoreactive B-cells that secrete ACPA to assist in identifying the presence of them within the media in order to tune and control the level of expression of our therapeutic agent according to the condition of the patient as reflected by the amount of the autoreactive B-cells. Second, it is expressed on the surface of exosomes conjugated to lamp2b to direct them toward auto-reactive B-cells that secrete ACPA and aid in their fusion with BCR.Thus, the possibility of delivering our therapeutic agent to the target cells is markedly improved as shown in figure 1 and figure 2.

Figure 1. illustrates the structure of the citrullinated vimentin (ccp1) within the extracellular domain of the Syn notch receptor expressed on the surface of the engineered MSC

Figure 1: This figure illustrates the construction of our engineered exosomes that express citrullinated vimentin on their membranes conjugated to a transmembrane protein known as lysosome-associated membrane glycoprotein 2b (lamp2b), which is unique to the membrane of exosomes.

Literature Characterization

Using sera from rheumatoid arthritis patients and healthy patients The study used gel electrophoresis and scatter diagrams to demonstrate the reactions of wild-type and mutant citrullinated vimentin.

A, There are 5 lanes containing blue staining of dodecyl sulfate-polyacrylamide gel of wild-type vimentin without peptidyl arginine deaminase treatment (lane 1), wild-type vimentin in the citrullinated form (lane 2), mutant vimentin without peptidyl arginine deaminase treatment (lane 3), and mutant vimentin in the citrullinated form (lane 4), while markers are located in lane 5. B, this is a scatter gram that demonstrates antibodies reactions against wild-type (wt), mutant (mv), and in vitro analogs (cwt,mcv). OD = optical density; NS = not significant.

References

Bang, H., Egerer, K., Gauliard, A., et al. Mutation and citrullination modifies vimentin to a novel autoantigen for rheumatoid arthritis. Arthritis Rheum. 56(8), 2503-2511 (2007). Sequence and Features