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J Autoimmunity: Modulation of T cell activation with antisense oligonucleotides targeting lymphocyte cytoplasmic protein 2

 Last Update: 2022-08-19
 Source: Internet
 Author: User

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Dysregulated T cell activation is a hallmark of several autoimmune diseases, such as rheumatoid arthritis (RA) and multiple sclerosis (MS.

The researchers identified a set of ASOs targeting the LCP2 3' UTR (designed to be 16 nucleotides long, integrating LNA (locked nucleic acid) nucleotides in a 3-10-3 spacer configuration with fully phosphorothioate (PS) modified backbone), which knocked down LCP2 in the human T cell line Jurkat cells and primary human T cells (monocytes isolated from healthy humans), and found that these inhibited T cell receptor-mediated The induced activation, including the attenuation of NF-κB activation, decreased the mRNA and protein levels of CD69 and CD25 in human T lymphocyte line Jurkat cell.

Taken together, the data from this study provide an example of how to develop immunomodulatory ASOs that interfere with non-druggable targets, and suggest that such drug modalities can be used to treat autoimmune disease.

Credit: Iyer VS, Boddul SV, Johnsson AK, Raposo B, Sharma RK, Shen Y, Kasza Z, Lim KW, Chemin K, Nilsson G, Malmström V, Phan AT, Wermeling .

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