Abstract
Cell-penetrating peptides (CPPs), which can facilitate the transport of molecular cargo across the plasma membrane, have become important tools in promoting the cellular delivery of macromolecules. GV1001, a peptide derived from a reverse-transcriptase subunit of telomerase (hTERT) and developed as a vaccine against various cancers, reportedly has unexpected CPP properties. Unlike typical CPPs, such as the HIV-1 TAT peptide, GV1001 enabled the cytosolic delivery of macromolecules such as proteins, DNA and siRNA via extracellular heat shock protein 90 (eHSP90) and 70 (eHSP70) complexes. The eHSP-GV1001 interaction may have biological effects in addition to its cytosolic delivery function. GV1001 was originally designed as a major histocompatibility complex (MHC) class II-binding cancer epitope, but its CPP properties may contribute to its strong anti-cancer immune response relative to other telomerase peptide-based vaccines. Cell signaling via eHSP-GV1001 binding may lead to unexpected biological effects, such as direct anticancer or antiviral effects. In this review, we focus on the CPP effects of GV1001 bound to eHSP90 and eHSP70.
Highlights
A number of biopharmaceuticals, including peptides, proteins, DNA and siRNA, are being considered as therapeutic agents that target intracellular molecules
We mainly focus on the cell-penetrating peptides (CPPs) effects of the GV1001-extracellular heat shock protein 90 (eHSP90) and -eHSP70 complexes
Unlike typical CPPs, such as the human immunodeficiency virus (HIV)-1 TAT peptide, GV1001 enables the cytosolic delivery of such macromolecules as proteins, DNA and siRNA via eHSP90 or eHSP70 complexes
Summary
A number of biopharmaceuticals, including peptides, proteins, DNA and siRNA, are being considered as therapeutic agents that target intracellular molecules. GV1001 exhibits biological activities beyond its use as a cancer vaccine, including as an anti-inflammatory agent [14], as a direct anticancer drug [15], as an anti-apoptotic and antioxidant compound [16] and as an antiviral [17,18]. In contrast to other CPPs, which penetrate the cell membrane through electrostatic interactions with proteoglycans, GV1001 permits the cytosolic delivery of macromolecules such as proteins, DNA and siRNA via extracellular heat shock protein 90 (eHSP90) and 70 (eHSP70) complexes [19]. Cell signaling via eHSP-GV1001 binding can lead to unexpected biological effects, such as direct anticancer activity [15] or antiviral effects against HCV [17] and HIV [18]. We mainly focus on the CPP effects of the GV1001-eHSP90 and -eHSP70 complexes
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