Combination of cell penetrating peptides and heterologous DNA prime/protein boost strategy enhances immune responses against HIV-1 Nef antigen in BALB/c mouse model

Improvements in chemical carriers of proteins and peptides

“…For instance, CPPs (e.g., Tat, penetratin, octaarginine, and PenetraMax) enhanced the intestinal absorption of dextran as a model cargo in rat and their efficiency changed according to the molecular size of dextran. Moreover, our findings indicated that the use of Tat (PTD) linked to HIV-1 Nef antigen in heterologous DNA prime/ protein boost strategy along with Gp96 adjuvant and Cady-2 CPP could significantly induce high levels of IgG2a and IFN-g directed toward Th1 responses and also cytotoxic T lymphocytes (CTLs) activity (Kurzawa et al, 2010;Kadkhodayan et al, 2017). Other study indicated an effective fusion-peptide-based delivery of alcohol dehydrogenase (ADH, 150 kDa) into intact Arabidopsis thaliana (Ng et al, 2016).…”

“…Although the mechanism of cellular uptake for the CPPs is still unknown, their structural properties and interactions with membrane phospholipids could play a major role in the cellular uptake mechanism. Some short amphipathic CPPs such as PEP and CADY families were also indicated to deliver therapeutic proteins or peptides through the formation of stable non-covalent complexes (Kadkhodayan et al, 2017). High negative surface charge of tumor cell membrane is involved in its invasive properties.…”

“…One disadvantage of protein transduction using PTDs is the entrapment of the PTD-fused protein within the endosomal vesicles (Yamaguchi et al, 2011). A short amphipathic peptide carrier, Pep-1 was used to deliver various therapeutic proteins including protein kinase A, MP51, elastin, cyclindependent kinases p27Kip, SOD, CAT, GDNF, peroxir-edoxin2, paraoxonase-1 (PON1), Methionine sulfoxide reductase A (MsrA), and human papillomavirus (HPV) E7 in cell cultures or animal model (Kurzawa et al, 2010;Kadkhodayan et al, 2017). The recent studies demonstrated that CPPs could safely and effectively increase the intestinal absorption of protein and peptide drugs in a non-covalent drug/CPP fashion.…”

“…Direct translocation, endocytotic processes and/or combination of several mechanisms were suggested as possible delivery pathways for CPPs (Eir ıksd ottir et al, 2010;Bolhassani, 2011;Bechara and Sagan, 2013;Borrelli et al, 2018). Some short amphipathic CPPs such as PEP and CADY families were also indicated to deliver therapeutic proteins or peptides through the formation of stable non-covalent complexes (Kadkhodayan et al, 2017). Protein transduction domains (PTDs) including HIV-1 Tat, pAntp43-58, and polyarginine (R9) are small peptides that are able to transport various peptides and proteins into several types of cells.…”

“…Some CPPs were able to form stable nanoparticles with proteins (e.g., PEP and CADY families) and efficiently transported cargoes into different cell lines in an endosomal-independent pathway. A short amphipathic peptide carrier, Pep-1 was used to deliver various therapeutic proteins including protein kinase A, MP51, elastin, cyclindependent kinases p27Kip, SOD, CAT, GDNF, peroxir-edoxin2, paraoxonase-1 (PON1), Methionine sulfoxide reductase A (MsrA), and human papillomavirus (HPV) E7 in cell cultures or animal model (Kurzawa et al, 2010;Kadkhodayan et al, 2017). Several advantages of the noncovalent complexes of Pep-1/cargo contain: (a) rapid delivery of proteins into cells with high efficiency; (b) stability in physiological buffers; and (c) lack of toxicity and sensitivity to serum.…”