Aptamer Selection Against IL21R for the Stimulation of Resistance to Type 1 Diabetes Mellitus

        Aptamer Selection Against IL21R for the Stimulation of Resistance to 
                                            Type 1 Diabetes Mellitus 
                                                 Lusaura Gutierrez 

           Type 1 diabetes mellitus is a disease brought about by the autoimmune attack and destruction of the beta cells located in the pancreas which causes an increase in blood glucose within the individual to occur. The autoimmune destruction of the pancreatic beta cells is in part provoked by the variation of CD8(+) T cells into Cytotoxic T Lymphocytes through the use of several cytokines, and transcription factors. Interleukin 21, a cytokine and growth factor for CD8(+) T cells, utilizes the T-bet transcription factor in order to promote Cytotoxic T Lymphocyte variation (Sutherland et al 2013). However, the Interleukin 21 receptor (Figure 1) functions as a controlling factor of antigen conveyance by dendritic cells in CD4(+) T cells which are required by CD8(+) T cells to effectively reach the pancreatic islets and induce diabetes (Van Belle et al 2012). Therefore, the hindering of the Interleukin 21 receptor (IL21R) would impair CD4(+)and CD8(+) T cells and consequently stimulate resistance to type 1 diabetes mellitus.
         A RNA aptamer, is a nucleic acid sequence that has been developed to recognize and bind with a high affinity and specificity to a selected target. Therefore, due to the inability of pancreatic infiltration to occur without the presence of IL21R signals created in CD4(+) T cells, a RNA aptamer against IL21R will prevent the IL21R signals from reaching auto reactive CD8(+) T cells and initiating pancreatic infiltration.
         Utilized as therapeutics, RNA aptamers are able to impede a specific function or pathway of a targeted protein. An aptamer against the IL21R will inhibit pancreatic infiltration and therefore, the overall development of type 1 diabetes mellitus.
         Specific Aim 1: Develop an anti-IL-21R aptamer capable of inhibiting the IL21R signal, and stimulating resistance to type 1 diabetes mellitus.
Figure 1:
Figure 1 demonstrates the signal producing IL-21 and IL-21R relationship in the CD4(+) T cells which are then transported to CD8(+) T cells for pancreatic infiltration, adapted from Rochman (2009).
Target order Information: 
Vendor: R & D Systems
Product catalog number: 991-R2-100
Vendor website: www.rndsystems.com
Vendor telephone number: (800) 343-7475
Cost per unit:  $319 per 100 ug
Cost per round: ~$32.98 ($16.49 per 100 pmol)

Sutherland AP, N. Joller, M. Michaud, SM Liu, VK Kuchroo, MJ Grusby. 2013. IL-21 Promote
            CD8(+) CTL Activity Via the Transcription Factor T-Bet.Journal of Immunology

Van Belle Tom, S.Nierkens, R. Arens, M. Von Herrath. 2012. Interleukin 21Receptor-Mediated
            Signals Control Autoreactive T Cell Infiltration in Pancreatic Islets. Immunity 


Click here for full proposal 
Click here for the first progress report 
Click here for the second progress report 
Click here for the final report 

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