Interferon α2–Thymosin α1 Fusion Protein (IFNα2–Tα1): A Genetically Engineered Fusion Protein with Enhanced Anticancer and Antiviral Effect

Human interferon α2 (IFNα2) and thymosin α1 (Tα1) are therapeutic proteins used for the treatment of viral infections and different types of cancer. Both IFNα2 and Tα1 show a synergic effect in their activities when used in combination. Furthermore, the therapeutic fusion proteins produced through t...

Full description

Bibliographic Details
Main Authors: Muhammad Shahbaz Aslam, Syed Zohaib Javaid Zaidi, Rabail Hassan Toor, Iram Gull, Muhammad Mudassir Iqbal, Zaigham Abbas, Imran Tipu, Aftab Ahmed, Muhammad Amin Athar, Christian Harito, Sammer-ul Hassan
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:Materials
Subjects:
Online Access:https://www.mdpi.com/1996-1944/14/12/3318
id doaj-d0e01199489c4179a565f77f5e82dd3d
record_format Article
spelling doaj-d0e01199489c4179a565f77f5e82dd3d2021-07-01T00:15:49ZengMDPI AGMaterials1996-19442021-06-01143318331810.3390/ma14123318Interferon α2–Thymosin α1 Fusion Protein (IFNα2–Tα1): A Genetically Engineered Fusion Protein with Enhanced Anticancer and Antiviral EffectMuhammad Shahbaz Aslam0Syed Zohaib Javaid Zaidi1Rabail Hassan Toor2Iram Gull3Muhammad Mudassir Iqbal4Zaigham Abbas5Imran Tipu6Aftab Ahmed7Muhammad Amin Athar8Christian Harito9Sammer-ul Hassan10Institute of Biochemistry and Biotechnology, University of the Punjab, Quaid-i-Azam Campus, Lahore 54590, PakistanInstitute of Chemical Engineering and Technology, University of the Punjab, Lahore 54590, PakistanSchool of Biological Sciences, University of the Punjab, Quaid-i-Azam Campus, Lahore 54590, PakistanInstitute of Biochemistry and Biotechnology, University of the Punjab, Quaid-i-Azam Campus, Lahore 54590, PakistanInstitute of Biochemistry and Biotechnology, University of the Punjab, Quaid-i-Azam Campus, Lahore 54590, PakistanDepartment of Microbiology & Molecular Genetics, University of the Punjab, Quaid-i-Azam Campus, Lahore 54590, PakistanDepartment of Life Sciences, University of Management & Technology, Lahore 54770, PakistanSchool of Biological Sciences, University of the Punjab, Quaid-i-Azam Campus, Lahore 54590, PakistanInstitute of Biochemistry and Biotechnology, University of the Punjab, Quaid-i-Azam Campus, Lahore 54590, PakistanIndustrial Engineering Department, Faculty of Engineering, Bina Nusantara University, Jakarta 11480, IndonesiaBioengineering Research Group, Faculty of Engineering and Physical Sciences, University of Southampton, Southampton SO17 1BJ, UKHuman interferon α2 (IFNα2) and thymosin α1 (Tα1) are therapeutic proteins used for the treatment of viral infections and different types of cancer. Both IFNα2 and Tα1 show a synergic effect in their activities when used in combination. Furthermore, the therapeutic fusion proteins produced through the genetic fusion of two genes can exhibit several therapeutic functions in one molecule. In this study, we determined the anticancer and antiviral effect of human interferon α2–thymosin α1 fusion protein (IFNα2–Tα1) produced in our laboratory for the first time. The cytotoxic and genotoxic effect of IFNα2–Tα1 was evaluated in HepG2 and MDA-MB-231 cells. The in vitro assays confirmed that IFNα2–Tα1 inhibited the growth of cells more effectively than IFNα2 alone and showed an elevated genotoxic effect. The expression of proapoptotic genes was also significantly enhanced in IFNα2–Tα1-treated cells compared to IFNα2-treated cells. Furthermore, the HCV RNA level was significantly reduced in IFNα2–Tα1-treated HCV-infected Huh7 cells compared to IFNα2-treated cells. The quantitative PCR analysis showed that the expression of various genes, the products of which inhibit HCV replication, was significantly enhanced in IFNα2–Tα1-treated cells compared to IFNα2-treated cells. Our findings demonstrate that IFNα2–Tα1 is more effective than single IFNα2 as an anticancer and antiviral agent.https://www.mdpi.com/1996-1944/14/12/3318fusion proteinanti-proliferative effectantiviral effectgenotoxic effectrelative expression
collection DOAJ
language English
format Article
sources DOAJ
author Muhammad Shahbaz Aslam
Syed Zohaib Javaid Zaidi
Rabail Hassan Toor
Iram Gull
Muhammad Mudassir Iqbal
Zaigham Abbas
Imran Tipu
Aftab Ahmed
Muhammad Amin Athar
Christian Harito
Sammer-ul Hassan
spellingShingle Muhammad Shahbaz Aslam
Syed Zohaib Javaid Zaidi
Rabail Hassan Toor
Iram Gull
Muhammad Mudassir Iqbal
Zaigham Abbas
Imran Tipu
Aftab Ahmed
Muhammad Amin Athar
Christian Harito
Sammer-ul Hassan
Interferon α2–Thymosin α1 Fusion Protein (IFNα2–Tα1): A Genetically Engineered Fusion Protein with Enhanced Anticancer and Antiviral Effect
Materials
fusion protein
anti-proliferative effect
antiviral effect
genotoxic effect
relative expression
author_facet Muhammad Shahbaz Aslam
Syed Zohaib Javaid Zaidi
Rabail Hassan Toor
Iram Gull
Muhammad Mudassir Iqbal
Zaigham Abbas
Imran Tipu
Aftab Ahmed
Muhammad Amin Athar
Christian Harito
Sammer-ul Hassan
author_sort Muhammad Shahbaz Aslam
title Interferon α2–Thymosin α1 Fusion Protein (IFNα2–Tα1): A Genetically Engineered Fusion Protein with Enhanced Anticancer and Antiviral Effect
title_short Interferon α2–Thymosin α1 Fusion Protein (IFNα2–Tα1): A Genetically Engineered Fusion Protein with Enhanced Anticancer and Antiviral Effect
title_full Interferon α2–Thymosin α1 Fusion Protein (IFNα2–Tα1): A Genetically Engineered Fusion Protein with Enhanced Anticancer and Antiviral Effect
title_fullStr Interferon α2–Thymosin α1 Fusion Protein (IFNα2–Tα1): A Genetically Engineered Fusion Protein with Enhanced Anticancer and Antiviral Effect
title_full_unstemmed Interferon α2–Thymosin α1 Fusion Protein (IFNα2–Tα1): A Genetically Engineered Fusion Protein with Enhanced Anticancer and Antiviral Effect
title_sort interferon α2–thymosin α1 fusion protein (ifnα2–tα1): a genetically engineered fusion protein with enhanced anticancer and antiviral effect
publisher MDPI AG
series Materials
issn 1996-1944
publishDate 2021-06-01
description Human interferon α2 (IFNα2) and thymosin α1 (Tα1) are therapeutic proteins used for the treatment of viral infections and different types of cancer. Both IFNα2 and Tα1 show a synergic effect in their activities when used in combination. Furthermore, the therapeutic fusion proteins produced through the genetic fusion of two genes can exhibit several therapeutic functions in one molecule. In this study, we determined the anticancer and antiviral effect of human interferon α2–thymosin α1 fusion protein (IFNα2–Tα1) produced in our laboratory for the first time. The cytotoxic and genotoxic effect of IFNα2–Tα1 was evaluated in HepG2 and MDA-MB-231 cells. The in vitro assays confirmed that IFNα2–Tα1 inhibited the growth of cells more effectively than IFNα2 alone and showed an elevated genotoxic effect. The expression of proapoptotic genes was also significantly enhanced in IFNα2–Tα1-treated cells compared to IFNα2-treated cells. Furthermore, the HCV RNA level was significantly reduced in IFNα2–Tα1-treated HCV-infected Huh7 cells compared to IFNα2-treated cells. The quantitative PCR analysis showed that the expression of various genes, the products of which inhibit HCV replication, was significantly enhanced in IFNα2–Tα1-treated cells compared to IFNα2-treated cells. Our findings demonstrate that IFNα2–Tα1 is more effective than single IFNα2 as an anticancer and antiviral agent.
topic fusion protein
anti-proliferative effect
antiviral effect
genotoxic effect
relative expression
url https://www.mdpi.com/1996-1944/14/12/3318
work_keys_str_mv AT muhammadshahbazaslam interferona2thymosina1fusionproteinifna2ta1ageneticallyengineeredfusionproteinwithenhancedanticancerandantiviraleffect
AT syedzohaibjavaidzaidi interferona2thymosina1fusionproteinifna2ta1ageneticallyengineeredfusionproteinwithenhancedanticancerandantiviraleffect
AT rabailhassantoor interferona2thymosina1fusionproteinifna2ta1ageneticallyengineeredfusionproteinwithenhancedanticancerandantiviraleffect
AT iramgull interferona2thymosina1fusionproteinifna2ta1ageneticallyengineeredfusionproteinwithenhancedanticancerandantiviraleffect
AT muhammadmudassiriqbal interferona2thymosina1fusionproteinifna2ta1ageneticallyengineeredfusionproteinwithenhancedanticancerandantiviraleffect
AT zaighamabbas interferona2thymosina1fusionproteinifna2ta1ageneticallyengineeredfusionproteinwithenhancedanticancerandantiviraleffect
AT imrantipu interferona2thymosina1fusionproteinifna2ta1ageneticallyengineeredfusionproteinwithenhancedanticancerandantiviraleffect
AT aftabahmed interferona2thymosina1fusionproteinifna2ta1ageneticallyengineeredfusionproteinwithenhancedanticancerandantiviraleffect
AT muhammadaminathar interferona2thymosina1fusionproteinifna2ta1ageneticallyengineeredfusionproteinwithenhancedanticancerandantiviraleffect
AT christianharito interferona2thymosina1fusionproteinifna2ta1ageneticallyengineeredfusionproteinwithenhancedanticancerandantiviraleffect
AT sammerulhassan interferona2thymosina1fusionproteinifna2ta1ageneticallyengineeredfusionproteinwithenhancedanticancerandantiviraleffect
_version_ 1721349140894449664