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A Novel Molecular Design for a Hybrid Phage-DNA Construct Against DKK1
Authors:Saeed Khalili  Mohamad Javad Rasaee  Taravat Bamdad  Maysam Mard-Soltani  Majid Asadi Ghalehni  Abolfazl Jahangiri  Mohammad Hassan Pouriayevali  Mohammad Reza Aghasadeghi  Fatemeh Malaei
Affiliation:1.Department of Biology Sciences,Shahid Rajaee Teacher Training University,Tehran,Iran;2.Department of Medical Biotechnology, Faculty of Medical Sciences, School of Medical Sciences,Tarbiat Modares University,Tehran,Iran;3.Department of Virology, School of Medical Sciences,Tarbiat Modares University,Tehran,Iran;4.Department of Clinical Biochemistry, Faculty of Medical Sciences,Dezful University of Medical Sciences,Dezful,Iran;5.Department of Medical Biotechnology, School of Advanced Technologies in Medicine,Tehran University of Medical Sciences,Tehran,Iran;6.Applied Microbiology Research Center, Systems Biology and Poisonings Institute,Baqiyatallah University of Medical Sciences,Tehran,Iran;7.Department of Hepatitis and AIDS,Pasteur Institute of Iran,Tehran,Iran
Abstract:Nucleic acid immunization has recently exhibited a great promise for immunotherapy of various diseases. However, it is now clear that powerful strategies are imminently needed to improve their efficiency. In this regard, whole bacteriophage particles have been described as efficient DNA vaccine delivery vehicles, capable of circumventing the limitations of naked DNA immunization. Moreover, phage particles could be engineered to display specific peptides on their surfaces. Given these inherent characteristics of phages, we have designed a novel hybrid phage-DNA immunization vector using both M13 and pAAV plasmid elements. Following the construction and in vitro confirmation of the designed vectors, they were used for comparative mice immunization, carrying the same DNA sequence. The results indicated the efficacy of the designed hybrid phage particles, to elicit higher humoral immunity, in comparison to conventional DNA-immunization vectors (pCI). In light of these findings, it could be concluded that using adeno-associated virus (AAV) expression cassette along with displaying TAT peptide on the surface of the phage particle could be deemed as an appealing strategy to enhance the DNA-immunization and vaccination efficacy.
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