DescriptionA nucleic acids technology has evolved utilizing the specific recognition of nucleic acid sequences by biological nucleic acids and proteins. Efforts concentrate on gene silencing and other potential pharmaceutical applications. Long studied are “antisense” oligonucleotides. The idea is simple: Synthetic nucleic acid fragments are to bind stably and selectively to the mRNA of a pathogenic protein to block its expression. Unfortunately, in spite of an enormous input of money and labour, few oligonucleotide pharmaceuticals are on the market, of which only one is truly based on the antisense principle. The reason is, that these developments have met with a number of serious problems: 1. Extraneous nucleic acids are usually rapidly degraded in cells and body fluids. Therefore, antisense oligonucleotides have to be structurally modified in order to avoid breakdown. 2. A pathogenic protein can only be effectively eliminated, if the respective mRNA is irreversibly degraded. Ribonuclease H, for instance, cleaves DNA-RNA hybrid double strands, but often not recognizes complexes of mRNA with structurally modified oligonucleotides. 3. The efficient and targeted cellular uptake of antisense oligonucleotides is still a problem.;;This report focuses on two developments from our research: (1.) Methods have been developed to promote the internalization of oligonucleotides (a) by conjugation with “cell penetrating peptides”, (b) by the application of oligonucleotide-loaded nanoparticles. (2.) Since for the solid-phase production of oligonucleotide drugs the polymeric carrier is a major cost factor, supports with unusually high loading capacity have been developed. Such carriers can contain 400 µmol nucleotides per gram, still maintaining ca. 99% yield of stepwise chain elongation.;;Talk introduced by Mostafa Zedan.
H. Seliger: Study of Chemistry. Ph.D. 1966 on "Approaches to the Synthesis of Oligonucleotides on Polymeric Supports" at the Max-Planck-Institute für Experimentelle Medizin in Göttingen (supervisor: F. Cramer). 1968 - 1969 Postdoctoral Fellow at Northwestern University, Evanston, USA (with R.L. Letsinger). 1969 - 1976 Assistant in the Institute for Macromolecular Chemistry, University of Freiburg (Hermann-Staudinger Institute, with Prof. E. Husemann). Habilitation for Macromolecular Chemistry. 1976 - 2002 Professor and Head of the Polymer Division of the University of Ulm. 2002 (official retirement) - 2008 Provisional head of the Division of Chemical Functions in Biosystems at the University of Ulm, later Research Group of Chemical Functions in Biosystems. 2009 - 2011 Director of the Laboratory for Chemical Functions in Biosystems, working for Antisense Pharma Co., in the Biotechnology Center of the “Technologie Foerderungs-Unternehmen GmbH” (TFU) in Ulm. since 2002 Founding Dean for Biotechnology in the Faculty of Pharmacy and Biotechnology of the German University in Cairo. Teaching: 1979 - 2008: Polymer Chemistry, focus on Biopolymers. Biomaterials. Biochemistry. Introductory and Advanced Practical Courses on Polymer Chemistry. 1990 -2000: Organizer and Chairman of the Graduate Study Program “Biomolecular Medicine”. 2000, 2001: Introduction to Combinatorial Nucleic Acid Synthesis; Oligonucleotide Libraries and their Applications. Since 2004: Lecture “Principles of Macromolecular Chemistry Determine the Behaviour of Biomaterials as well as of Synthetic Polymers” in the International Master Course “Advanced Materials” at the University of Ulm. Since 2003: Lectures on “Colours of Biotechnology” and on “Some Basic Principles of Biopolymers” at the German University in Cairo. Research: Synthesis of oligo- and polynucleotides mainly with application of the solid-phase technique. Structurally modified oligonucleotides of potential therapeutic interest. Combinatorial nucleic acid chemistry. Oligonucleotide-loaded nanoparticles. Synthesis of bio-polyester-urethanes on the basis of renewable resources, in particular biogenic poly-3-hydroxy-alkanoates.
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