Peptoplexes as artificial viruses for nucleic acid vaccine delivery

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ABSTRACT Nucleic acid vaccines encode subunit antigens on DNA or mRNA level which, following transfection of target cells, can be expressed and processed like conventional peptide antigens. Based on the current state of knowledge, this class of vaccines seems especially promising in the context of tumor immunotherapy. The present work describes the establishment of a novel class of non-viral vectors which are based on polypept(o)ides as underlying material and are capable to deliver nucleic acid vaccines into dendritic cells. In the context of medical application, polypept(o)ides hold great promise as a source material for the formation of biocompatible nanoparticles, since they combine high stability in aqueous solution, unique secondary structures and the intrinsic multifunctionality of the amino acids with enzymatic degradability. In order to bring nuceic acids into an intravenous administration form, the polypept(o)ides developed in this work are designed to condense pDNA or mRNA into polyplexes with core-shell architecture (PeptoPlexes). Introducing nucleic acids into non-dividing cells like dendritic cells is a challenging procedure. Thus, throughout the PhD thesis, polypept(o)ides and PeptoPlexes were constantly refined and functionality of the systems was increased successively. Methods applied for the development of PeptoPlexes involved organic and polymer synthesis, physicochemical characterization, biochemistry, microscopy studies, cell biology and animal studies. Eventually, the latest generation of PeptoPlexes succeeded in the transfection of dendritic cells by mimicking key functions of viruses, namely, targeted cellular uptake, stimuli-responsive disassembly, endosomal escape and nuclear import of the genetic code. Preliminary in vivo experiments indicate a favorable biodistribution of PeptoPlexes. . . KURZDARSTE L LUNG

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