A Novel Molecular Design for a Hybrid Phage-DNA Construct Against DKK1

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.

Atezolizumab and granzyme B as immunotoxin against PD-L1 antigen; an insilico study

“…Even models with low accuracy could be useful to make assumptions about the ctional model of an unknown antigen (13,14). Using molecular modeling methods would help the researchers to decrease the number of necessary experimental assessments and to avoid different ethical issues (15)(16)(17)(18). Given these properties of molecular modeling methods, we have launched an in silico study to model and assess an immunotoxin for its functionality against PD-L1 molecule.…”

Drug Discovery of DKK1 Inhibitors

“… Zhang et al (2015a) constructed a multiepitope DNA vaccine against DKK1 by screening and optimizing four B cell epitopes; the results implied that vaccination could attenuate bone erosion relevant to DKK1 in collagen-induced arthritis (CIA) mice and lower the disease incidence of arthritis in CIA-susceptible mice. To further facilitate the efficiency of the DNA vaccine and circumvent the limitations of the conventional DNA-immunization approach, a novel hybrid phage particle was used to carry the DKK1 gene ( Khalili et al, 2018 ). The phage-immunization results showed higher efficiency of the immunization vehicle and stronger humoral immune responses in contrast to classical DNA-immunization vectors, which meant that larger amounts of antibodies against DKK1 were produced.…”