Rheumatoid Arthritis (RA) is an autoimmune disease and chronic inflammatory disorder that affects joints and causes inflammation, pain, stiffness, and eventually progressive joint destruction. Approximately 1% of the world's population is estimated to suffer from RA, and if this disease is left untreated, it can lead to severe disability. Despite all the efforts and advances made by professionals in the field, there is currently no definitive treatment for RA, and most treatment strategies are aimed at relieving symptoms and improving patients' quality of life. One of the most promising current approaches is the use of recombinant proteins that target specific signaling pathways involved in the development of RA to alleviate symptoms and slow the progression of the disease. This article discusses the genetic and immunological factors that influence the development of RA, recombinant proteins, methods of using these proteins, approved drugs, and side effects associated with treating RA.

Background: The main problem in the recombinant protein expression in E. coli strains, especially for high-yield production, is the accumulation in un-folded and inactive inclusion bodies. A suitable solution is the direction into the soluble cytoplasmic products by solubilizing tags. The use of inteins with self-cleaving ability, in addition to increase the chance of soluble protein expression, facilitates their purification process. Evidence Acquisition: In this review article, papers related to the use of intein tags for soluble expression or protein purification were collected regardless the time limit. Available databases  including Pubmed, google scholar, ScienceDirect, Web of Science, Scopus, and Embase was searched. The best condition for soluble expression or purification was focused in all articles. Results: There are various intein tags commercially available in expression vectors that results in gaining our goal in facilitating the recombinant protein solubilization as well as its simple purification. It is enough to induce the self-cleavage property of the intein, which varies according to the type of intein used. In this way, the target protein is easily separated from the purification tag without the need to add protease enzymes such as enterokinase or treatment with various chemicals. The most common affinity tag in intein-based systems is Chitin Binding Domain attached to the chitin resin. Conclusions: In this review article, we introduced proteins or peptides which produced in fusion to intein tags and discussed about their expression condition and purification process in order to enhance the chance of soluble expression and intein cleavage in a single stage, respectively.

A specific protein is rarely easily enriched from natural host cells. Therefore, recombinant protein production is the only practical procedure. Different recombinant proteins have been produced in prokaryotic hosts but many of them accumulate in the form of inactive inclusion bodies. The inability of prokaryotes to produce native versions of eukaryotic proteins is because of unsuitable posttranslational protein processing, including inappropriate protein cleavage and folding, and to the lake of proper mechanisms that add chemical groups to specific amino acids. Consequently, eukaryotic expression systems were devised for fungal, insect, mammalian cells, and plant hairy roots. Although functional recombinant proteins have been achieved using fungal and insect cells, some mammalian proteins are not correctly glycosylated. In the other side, the mammalian host cells have the high costs. All of these cell hosts can become contaminated with the animal pathogens and sometimes are so costly and complex to be optimized. Hence, hairy roots for recombinant protein production are as one of the interesting technologies. They result from the genetic transformation of plant cells after infection by Agrobacterium rhizogenes. They have interesting advantages including fast growth rate on hormone-free medium, highly branched, and phenotypically and genetically stability. Hairy roots can do all the posttranslational protein processing. The foreign proteins expressed are usually secreted in the culture medium and can be harvested from it with the low cost. This model of recombinant protein production is relatively safe because they are non-host for animal pathogens.