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Cell Journal، جلد ۲۱، شماره ۴، صفحات ۴۳۳-۴۴۳
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عنوان انگلیسی Biosimilar Gene Therapy: Investigational Assessment of Secukinumab Gene Therapy
چکیده انگلیسی مقاله Objective
Tumor necrosis factor-alpha (TNF-α), checkpoint inhibitors, and interleukin-17 (IL-17) are critical targets in inflammation and autoimmune diseases. Monoclonal antibodies (mAbs) have a successful portfolio in the treatment of chronic diseases. With the current progress in stem cells and gene therapy technologies, there is the promise of replacing costly mAbs production in bioreactors with a more direct and cost-effective production method inside the patient’s cells. In this paper we examine the results of an investigational assessment of secukinumab gene therapy.
Materials and Methods
In this experimental study, the DNA sequence of the heavy and light chains of secukinumab antibodies were cloned in a lentiviral vector. Human chorionic villous mesenchymal stem cells (CMSCs) were isolated and characterized. After lentiviral packaging and titration, part of the recombinant viruses was used for transduction of the CMSCs and the other part were applied for systemic gene therapy. The engineered stem cells and recombinant viruses were applied for ex vivo and in vivo gene therapy, respectively, in different groups of rat models. In vitro and in vivo secukinumab expression was confirmed with quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and ELISA by considering the approved secukinumab as the standard reference.
Results
Cell differentiation assays and flow cytometry of standard biomarkers confirmed the multipotency of the CMSCs. Western blot and qRT-PCR confirmed in vitro gene expression of secukinumab at both the mRNA and protein level. ELISA testing of serum from treated rat models confirmed mAb overexpression for both in vivo and ex vivo gene therapies.
Conclusion
In this study, a lentiviral-mediated ex vivo and in vivo gene therapy was developed to provide a moderate dose of secukinumab in rat models. Biosimilar gene therapy is an attractive approach for the treatment of autoimmune disorders, cancers and other chronic diseases.
کلیدواژه‌های انگلیسی مقاله Gene therapy, genetic vectors, monoclonal antibody, Secukinumab, Stem cells
نویسندگان مقاله Ali Fallah |
Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran;RNAx Ltd., London, UK

Hajar Estiri |
RNAx Ltd., London, UK

Elizabeth Parrish |
RNAx Ltd., London, UK

Mansoureh Soleimani |
Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran

Sirous Zeinali |
4Molecular Medicine, Pasteur Institute of Iran, Tehran, Iran

نشانی اینترنتی https://www.celljournal.org/article_250608_9b98a39233527c499bd36ceef95ccff9.pdf
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