Selection and characterization of a new human Interleukin-17A blocking DNA aptamer using protein-SELEX.

BACKGROUND: Interleukin-17A (IL-17A) is an important pro-inflammatory cytokine observed in the development of many disorders, such as psoriasis, rheumatoid arthritis, and multiple sclerosis. The anti-IL-17A biological drugs, including Secukinumab, Ixekizumab, and Brodalumab, are monoclonal antibodies approved for several disease treatments. Due to the disadvantages of biological therapies, including their immunogenicity, difficulties in scale generation, and high production costs and time, it is necessary to find new alternative anti- IL-17A agents for these monoclonal antibodies. Our study aimed to identify ssDNA aptamers that block IL-17A activity using the protein-SELEX procedure. METHODS: The hIL-17A was expressed in codon plus E. coli, and after 14 rounds of the SELEX process, monitoring of aptamer pools was done using the dot blot method. Three families of aptamers were obtained from the selected round 9 aptamer pool, and seven truncates were created. Inhibitory effects of aptamer truncate on IL-17-induced CCL20 expression in HaCaT keratinocytes were evaluated. RESULTS: All aptamer truncates had a significant inhibitory effect compared to the library, but the inhibitory effect of M2 and M7 truncates was more than 80%. Moreover, we evaluated the potential binding site of selected aptamers by ELISA. CONCLUSIONS: We introduced a new small 17-nucleotide DNA aptamer that efficiently binds and blocks hIL-17A with a 0.3 nM kd, a potential anti-IL-17A therapeutic agent.

Plaque-type psoriasis inhibitors.

Psoriasis is a common inflammatory skin disorder, which is mediated by the immune system and affects 1-4% of the world's population. Psoriasis is caused by a complex interaction between the immune system, autoantigens, psoriasis-associated genetic factors, and various environmental factors. As a chronic disease requiring long-term treatment, psoriasis is associated with follow-up costs and an economic burden on the patients, their families, and healthcare systems. The current treatments for moderate-to-severe plaque psoriasis include topical therapy, phototherapy, and systemic drugs consisting of biological/non-biological drugs. Within the past two decades, recent biological therapies for psoriasis have rapidly advanced. Moreover, new bispecific agents have the potential for better disease control, while small molecule drugs offer a future alternative to biological drugs and the more cost-effective, long-term treatment of the disease. The present study aimed to review updated data regarding the inhibitors used to improve plaque psoriasis that contain biologics, bispecific agents, small molecules, and aptamers (either approved or in the research phase).