Moreover, in both COS-7 and RCS cells, shRNA 3B reduced the elevated CRT levels that result from the overexpression of COMP. Taken together, these results suggest that reducing mutant COMP mRNA levels may dampen the ER stress and matrix formation in the rER that is potentiated by the presence of mutant COMP. Overall, we show that suppression of COMP expression by RNAi in vitro would be an effective treatment modality for the PSACH and MED/EDM1 chondrocyte pathology. This work provides a proof of principle for the potential development of treatment for this ER storage disorder. Delivery of RNAi therapy to avascular tissues, such as cartilage may be a challenge. In one approach, the delivery of siRNA molecules to bone metastatic tumors was mediated by their attachment to bovine pepsin treated type I collagen. This complex was infused and taken up by the tumor. Future delivery mechanisms that target cartilaginous tissue and/or chondrocytes need to be developed. The long-term goal for a treatment modality for PSACH and MED/EDM1 is to prevent premature chondrocyte loss and restore chondrocyte function, which is necessary for normal bone growth and ECM integrity. Of the millions of proteins residing in public repositories only a small percentage have had their functions determined Oleanolic experimentally. The vast majority of proteins have been annotated through predictive methods which work by comparing protein sequences and determining their degree of similarity. This is carried out by computer programs such as BLAST or various other tools and databases. This Norcantharidin process, where a protein of unknown function receives the function from a known protein, has been described as ����annotation transfer����. The rationale being that proteins of similar sequence fold into similar protein structures which therefore perform similar biological functions. However, in spite of much research more needs to be done to improve the accuracy of function prediction. There is also a huge and burgeoning population of ����hypothetical���� proteins with only moderate similarity to proteins of known function. Limitations of current approaches in this moderate similarity range, make it extremely difficult to annotate proteins of this type reliably.