Biosimilar Gene Therapy: Investigational Assessment of Secukinumab Gene Therapy

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FALLAH ALI; ESTIRI HAJAR; Parrish Elizabeth; SOLEIMANI MANSOUREH; ZEINALI SIROUS; ZADEH VAKILI AZITA

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Journal Paper

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Journal: Cell Journal (Yakhteh) Year:2020 | Volume:21 | Issue:4 Page(s): 433-443

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Title

Biosimilar Gene Therapy: Investigational Assessment of Secukinumab Gene Therapy

Author(s)

Keywords

Gene Therapy

Genetic Vectors

Monoclonal Antibody

Secukinumab

Stem Cells

Abstract

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.

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APA: Copy

FALLAH, ALI, ESTIRI, HAJAR, Parrish, Elizabeth, SOLEIMANI, MANSOUREH, ZEINALI, SIROUS, & ZADEH VAKILI, AZITA. (2020). Biosimilar Gene Therapy: Investigational Assessment of Secukinumab Gene Therapy. CELL JOURNAL (YAKHTEH), 21(4), 433-443. SID. https://sid.ir/paper/719635/en

Vancouver: Copy

FALLAH ALI, ESTIRI HAJAR, Parrish Elizabeth, SOLEIMANI MANSOUREH, ZEINALI SIROUS, ZADEH VAKILI AZITA. Biosimilar Gene Therapy: Investigational Assessment of Secukinumab Gene Therapy. CELL JOURNAL (YAKHTEH)[Internet]. 2020;21(4):433-443. Available from: https://sid.ir/paper/719635/en

IEEE: Copy

ALI FALLAH, HAJAR ESTIRI, Elizabeth Parrish, MANSOUREH SOLEIMANI, SIROUS ZEINALI, and AZITA ZADEH VAKILI, “Biosimilar Gene Therapy: Investigational Assessment of Secukinumab Gene Therapy,” CELL JOURNAL (YAKHTEH), vol. 21, no. 4, pp. 433–443, 2020, [Online]. Available: https://sid.ir/paper/719635/en

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