The molecular weight of DNA, RNA or oligonucleotides to be delivered by gene therapy is too large and has a large number of negative charges, so it is difficult to reach target tissues and cells to play a role. Therefore, safe and effective gene delivery vectors have become the key to gene therapy. Viral vectors are currently the most widely used and most efficient clinically. However, due to their toxicity, immunogenicity, carcinogenesis, and difficulty in large-scale production, scientists have been solving these problems by designing non-viral vectors. Compared with polymers and liposomes (LNP), polypeptides have become a promising class of non-viral vectors due to their better biocompatibility, tissue targeting, functional diversity, and ease of synthesis and modification.
Polypeptide gene carriers usually contain multiple lysine or arginine residues, which are positively charged at physiological pH, bind to nucleic acids through electrostatic interactions, then interact with cell membranes, and enter cells. Hydrophobic amino acid residues or hydrophobic components (such as alkyl chains) in polypeptides are conducive to their self-assembly to form nanoparticles or fibers and can promote their interaction with cell membranes. The introduction of histidine residues into the polypeptide sequence can also enhance endosomal escape through the proton sponge effect, thereby improving delivery efficiency.
Peptide vaccines are vaccines prepared by chemical synthesis techniques according to the amino acid sequence of a known or predicted epitope in the pathogen antigen gene.
Tumor therapeutic polypeptide vaccine is one of the important directions. The difference between tumor cells and normal cells can be described in thousands of ways, but the most fundamental difference is due to the mutation of tumor cells. Many tumor cells have various mutations, and some mutations are presented to the surface of tumor cells through MHC, and then specifically recognized by the TCR of T cells, thereby directly killing tumor cells. Such mutant peptides are called new peptides. Antigen (neoantigen). If specific neoantigens in tumor cells can be found and cancer vaccines can be developed based on this amino acid sequence, relevant immune cells can be activated to kill tumor cells with the same antigen. Current challenges such as poor immunogenicity and efficacy limited by HLA phenotype.
Prophylactic peptide vaccines will be a much needed emerging field. From inactivated vaccines to recombinant protein vaccines to mRNA vaccines, immunocompromised people cannot get enough protection, and a paper in the journal Nature on November 24, 2021 gives us hope to make up for the loophole [Nature. 2022, 601, 617-622]. A peptide novel coronavirus vaccine named CoVac-1 led by the University of Tübingen in Germany has shown good safety, reactogenicity and immunogenicity in phase I clinical trials, and it is effective against various current mutant strains. All have good protective effect. Currently, Phase II clinical trials for the vaccine are underway. The main active ingredient of this vaccine is the specific T cell epitope from a variety of new coronavirus proteins (including the familiar spike protein and nucleoprotein shell, membrane glycoprotein, envelope glycoprotein, etc.), which are similarly affected by Toll. Combined with the body agonist XS15, it is emulsified in the adjuvant, so that the vaccine can produce a persistent T cell response.