In vivo -targeting of therapeutic oligonucleotides

The goal is to provide targeted delivery of therapeutic oligonucleotides toward certain organs or cell types. One option is covalent conjugation of oligonucleotides with appropriate cell-targeting ligands. For this purpose various biologically active carbohydrates (e.g. hyaluronic acids, chondroitin sulphates, bleomycin disaccharide) and carbohydrate clusters are evaluated. The time-dependent biodistribution of the conjugates are studied in detail by in vivo PET-imaging in collaboration with Turku PET Centre.

In the ongoing project, the second generation delivery systems for oligonucleotides, based on the potential of self-assembled oligonucleotide-based nano constructs, are studied. It has clearly been demonstrated that self-assembled DNA-based nanoparticles with a well-defined size may improve cellular targeting and intracellular delivery of oligonucleotides. In addition to these beneficial delivery properties, the programmability of the structures seems highly attractive for the ligand-induced targeting. The size and the spatial orientation of the tertiary structure may be controlled precisely, which may be applied for the sugar-receptor mapping on the cell surface. The delivery potential of oligonucleotide-based nano constructs and of the ligand-induced targeting are hence be combined.

Related Publications

  1. Jadhav S., Käkelä M., Mäkilä J., Kiugel M., Liljenbäck H., Virta J., Poijärvi-Virta P., Laitala-Leinonen T., Kytö V., Jalkanen S., Saraste A., Roivainen A., Lönnberg H., Virta P. Bioconjugate Chem., 2016, 27, 391.
  2. Jadhav S., Yim C.-B., Rajander J., Grönroos T.J., Solin O., Virta P. Bioconjugate Chem. 2016, 27, 1023
  3. Jadhav S., Käkelä M., Mäkilä J., Rimpilä K., Laitala-Leinonen T., Poijärvi-Virta P., Lönnberg H., Roivainen A., Virta P. Mol. Pharm., 2016, 13, 2588.
  4. Mäkilä J., Jadhav S., Kiviniemi A., Käkelä M., Liljenback H., Poijärvi-Virta P., Laitala-Leinonen T., Lönnberg H., Roivainen A., Virta P. Bioorg. Med. Chem., 2014, 22, 6806.
  5. Kiviniemi A., Mäkelä J., Mäkilä J., Saanijoki T., Liljenback H., Poijärvi-Virta P., Lönnberg H., Laitala-Leinonen T., Roivainen A., Virta P. Bioconjugate Chem. 2012, 23, 1981.