## 1 Introduction  
Human insulin, the world's first genetically engineered drug, was approved by the U.S. Food and Drug Administration in 1982. Since then, the market for biopharmaceuticals has grown dramatically [1, 2]. Biopharmaceuticals are drug products synthesized or extracted from living organisms (including humans). Among them, recombinant therapeutic proteins such as monoclonal antibodies, hormones, vaccines, and enzymes occupy a large proportion [3, 4]. The Chinese hamster ovary (CHO) cell line is a widely used mammalian cell line for the production of recombinant therapeutic proteins [5]. The wide use of the CHO cell system can be attributed to the following reasons: many previous cases of approvals from regulatory agencies, the availability of large-scale suspension culture using a chemically defined medium, and the presence of very effective transgene amplification methods such as the dihydrofolate reductase (DHFR)-mediated system [6]. In addition, recombinant proteins produced from CHO cells exhibit similar glycosylation profiles to original human proteins, which is an important advantage as a platform for the production of therapeutic proteins due to the correlation between the glycan structures of glycoproteins and in vivo activities [7, 8, 9]. To increase protein productivity in recombinant CHO cells, several strategies have been employed. To improve the time integral of viable cell concentration and/or the specific productivity of a foreign protein, the optimization of various culture conditions (such as pH, dissolved oxygen and carbon dioxide, temperature, and osmol [10; 11; 12; 13]) and genetic engineering (including the overexpression of antiapoptotic proteins such as Bcl-xL, cell cycle-promoting, cyclin-dependent kinase homologs, and endoplasmic reticulum (ER)-resident chaperones [14; 15; 16]) have been studied extensively. Erythropoietin (EPO) is a representative therapeutic glycoprotein that has been manufactured in CHO cells. EPO, a glycoprotein composed of 165 amino acids and a type of hormone mainly produced in adult kidneys, plays a crucial role in stimulating the bone marrow to increase the number of red blood cells (RBCs) [17]. However, if a sufficient amount of EPO is not produced due to kidney injuries or when bone marrow is not stimulated by EPO, anemia can occur because RBCs are poorly produced [18]. Some studies have also shown that EPO is effective in promoting angiogenesis and anti apoptosis of ischemic tissues [19; 20]. Due to its therapeutic potential, recombinant EPO has been applied in clinical treatments for anemia due to chronic kidney disease and for decreasing the need for RBC transfusions in patients undergoing some types of surgery [21; 22]. Many studies have been conducted to improve the yield of EPO production in CHO cells. Our previous studies have demonstrated that the productivity of recombinant EPO in CHO cells can be improved not only by overexpressing the silkworm-derived _30 Kc19_ gene, but also by supplementing the culture medium with a recombinant 30 Kc19 protein produced in the _Escherichia coli_ (_E. coli_) expression system [23; 24]. 30 Kc19 is a type of plasma protein found in silkworm hemolymph and is a member of the structurally related 30K protein family. Among 30K proteins, 30 Kc19 has both cell-penetrating and protein-stabilizing properties [25; 26]. These findings suggest that the enhanced EPO productivity in recombinant CHO cells after the intracellular delivery of the 30 Kc19 protein is due to the stabilization of mitochondrial enzyme complexes responsible for electron transport and ATP generation [27]. Meanwhile, other studies have demonstrated that the \(\alpha\)-helix N-terminal domain of _30 Kc19_ (30 Kc19\(\alpha\)), dominantly expressed as a soluble form in _E. coli_, exhibits protein-stabilizing and cell-penetrating effects similar to or higher than the full-length 30 Kc19 protein [28; 29].