Dr. Markus Lamla

Title: Development of novel delivery systems for the transfer of drugs into cell compartments

Research Description: Dysfunctions in cellular compartments are causing several diseases. For example, mutations in the mitochondrial DNA (mtDNA) result in a variety of disorders, which particularly affect tissues with a high ATP turnover rate such as skeletal muscle and brain. Our strategy is to use peptide nucleic acids (PNAs) which bind specifically to the mutated mtDNA for the inhibition of mtDNA replication. PNAs are synthetic structural homologues of nucleic acids in which the negatively charged phosphate-sugar backbone of the polynucleotide is replaced by an uncharged polyamide backbone consisting of achiral N-(2-aminoethyl)glycine unit (see Fig. 1). Due to this structure PNAs binds to DNA and RNA with high affinity and specificity. For the cellular and mitochondrial uptake the PNAs are modified with two different peptides: with a cell penetrating peptide and with a mitochondrial targeting signal peptide.