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Engineered Exosomes for Targeted Transfer of siRNA to HER2 Positive Breast Cancer Cells

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Abstract

Exosomes are the best options for gene targeting, because of their natural, nontoxic, non-immunogenic, biodegradable, and targetable properties. By engineering exosome-producing cells, ligands can be expressed fusing with exosomal surface proteins for targeting cancer cell receptors. In the present study, HER2-positive breast cancer cells were targeted with a modified exosome producing engineered HEK293T cell. For this purpose, the HEK293T cells were transduced by a lentiviral vector bearing-LAMP2b-DARPin G3 chimeric gene. Stable cells expressing the fusion protein were selected, and the exosomes produced by these cells were isolated from the culture medium, characterized, and then loaded with siRNA for subsequent delivery to the SKBR3 cells. Our results showed that stable HEK293T cells produced DARPin G3 on the surface of exosomes. These exosomes can bind specifically to HER2/Neu and are capable of delivering siRNA molecules against TPD52 gene into SKBR3 cell line down-regulating the gene expression up to 70%. Present approach is envisaged to facilitate genes and drugs transfer to HER2 cancer cells providing additional option for gene therapy and drug delivery.

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Funding

This work was supported by educational program grant from Tarbiat Modares University and Iranian national science foundation: INSF (code No: 90006884).

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Authors and Affiliations

  1. Department of Medical Biotechnology, Faculty of Medical Science, Tarbiat Modares University, P.O.Box:14115-331 I.R, Jalal ale Ahmad Highway, Tehran, Iran

    Shabanali Khodashenas Limoni, Mehdi Forouzandeh Moghadam, Hosna Gomari & Fatemeh Salimi

  2. Immunogenetic Research Center, Mazandaran University of Medical Sciences, Sari, Iran

    Shabanali Khodashenas Limoni

  3. Department of Medical Immunology, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran

    Seyed Mohammad Moazzeni

Authors
  1. Shabanali Khodashenas Limoni
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  2. Mehdi Forouzandeh Moghadam
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  3. Seyed Mohammad Moazzeni
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  5. Fatemeh Salimi
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Correspondence to Mehdi Forouzandeh Moghadam.

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Limoni, S.K., Moghadam, M.F., Moazzeni, S.M. et al. Engineered Exosomes for Targeted Transfer of siRNA to HER2 Positive Breast Cancer Cells. Appl Biochem Biotechnol 187, 352–364 (2019). https://doi.org/10.1007/s12010-018-2813-4

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  • DOI: https://doi.org/10.1007/s12010-018-2813-4

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