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Host cell in vivo production of the synthetic drug anti–CD25/IL‐10 using minicircle vector
Author(s) -
Lim Sun Woo,
Shin Yoo Jin,
Luo Kang,
Quan Yi,
Ko Eun Jeong,
Chung Byung Ha,
Yang Chul Woo
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201900833r
Subject(s) - in vivo , il 2 receptor , minicircle , transplantation , secretion , biology , pharmacology , ex vivo , immunology , microbiology and biotechnology , medicine , t cell , immune system , biochemistry , gene
Synthetic biologic drugs are highly successful for induction therapy in transplantation, but the development of novel biologics is limited because of the high cost of synthesis and purification. In this study, we developed a novel strategy for the production of synthetic protein drugs in vivo by the host itself. We utilized minicircle (MC) technology, which can robustly express a target molecule and secrete it from cells, as an indirect method to produce a protein of interest in vivo . We designed an MC vector containing the sequences of basiliximab (anti‐CD25 mAb) and IL‐10. We verified the substantial production of the anti—CD25/IL‐10 protein from the MC in vitro and in vivo . The therapeutic effect of MC‐derived anti—CD25/IL‐10 was evaluated in a skin allograft mouse model by single intravenous infusion. Mice treated with the MC encoding anti—CD25/IL‐10 exhibited prolonged skin allograft survival times accompanied by improved histologic changes and immunologic regulation. These findings indicate that the anti—CD25/IL‐10 protein drug obtained by MC technology is functionally active and relevant for reducing allograft rejection. This self‐reproducible strategy for synthetic protein drugs using MCs is a promising tool for transplantation.—Lim, S. W., Shin, Y. J., Luo, K., Quan, Y., Ko, E. J., Chung, B. H., Yang, C. W. Host cell in vivo production of the synthetic drug anti‐CD25/IL‐10 using minicircle vector. FASEB J. 33, 10889–10901 (2019). www.fasebj.org