PMID- 31376325
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220409
IS  - 2228-5806 (Print)
IS  - 2228-5814 (Electronic)
IS  - 2228-5806 (Linking)
VI  - 21
IP  - 4
DP  - 2020 Jan
TI  - Biosimilar Gene Therapy: Investigational Assessment of Secukinumab Gene Therapy.
PG  - 433-443
LID - 10.22074/cellj.2020.6309 [doi]
AB  - OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha), 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.
CI  - Copyright(c) by Royan Institute. All rights reserved.
FAU - Fallah, Ali
AU  - Fallah A
AD  - Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid 
      Beheshti University of Medical Sciences, Tehran, Iran.
AD  - RNAx Ltd., London, UK.
FAU - Estiri, Hajar
AU  - Estiri H
AD  - RNAx Ltd., London, UK.
FAU - Parrish, Elizabeth
AU  - Parrish E
AD  - RNAx Ltd., London, UK.
FAU - Soleimani, Mansoureh
AU  - Soleimani M
AD  - Cellular and Molecular Research Center, Iran University of Medical Sciences, 
      Tehran, Iran.
FAU - Zeinali, Sirous
AU  - Zeinali S
AD  - Molecular Medicine, Pasteur Institute of Iran, Tehran, Iran.Electronic 
      Address:zeinali@pasteur.ac.ir.
FAU - Zadeh-Vakili, Azita
AU  - Zadeh-Vakili A
AD  - Cellular and Molecular Endocrine Research Center, Research Institute for 
      Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, 
      Iran.Electronic Address:azitavakili@endocrine.ac.ir.
LA  - eng
PT  - Journal Article
DEP - 20190729
PL  - Iran
TA  - Cell J
JT  - Cell journal
JID - 101566618
PMC - PMC6722441
OTO - NOTNLM
OT  - Gene Therapy
OT  - Genetic Vectors
OT  - Monoclonal Antibody
OT  - Secukinumab
OT  - Stem Cells
COIS- There is no conflict of interest in this study.
EDAT- 2019/08/04 06:00
MHDA- 2019/08/04 06:01
PMCR- 2020/01/01
CRDT- 2019/08/04 06:00
PHST- 2018/08/19 00:00 [received]
PHST- 2018/12/09 00:00 [accepted]
PHST- 2019/08/04 06:00 [entrez]
PHST- 2019/08/04 06:00 [pubmed]
PHST- 2019/08/04 06:01 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.22074/cellj.2020.6309 [doi]
PST - ppublish
SO  - Cell J. 2020 Jan;21(4):433-443. doi: 10.22074/cellj.2020.6309. Epub 2019 Jul 29.