Nucleic acids and peptides in biotechnology and therapy - Roger Strömberg
Oligonucleotide Based Artificial Nucleases and PNAzymes
Artificial enzymes are developed, including PNAzymes that are world leading artificial ribonucleases and the first truly artificial RNA restriction enzymes. These tailor-made RNases, are usable tools for molecular biology and is currently developed further to obtain a cleavage rate that may allow use in therapy.
Stabilised, Cell Penetrating and Target Seeking Oligonucleotides for Enhanced Therapy
A novel approach based on a synthetic 2,2,7-trimethylguanosine Cap (m3G-Cap) NLS and oligonucleotides (ONs) with an incorporated m3G-Cap gave enhanced splice correction. Modified m3G-CAP’s that are more resistant to degradation is now pursued. Another development is cell penetrating oligonucleotides (CPO) that are taken up spontaneously and also are highly resistant towards enzymatic degradation, which suggest high potential for use in ON therapy. Further developments includes designed nano-constructs that contain elements of recognition (ON), tissue targeting (e.g. homing peptides), cell permeation elements (CPO etc) and nuclear delivery signals.
Helix Stabilisers that Inhibit Aβ-Peptide Aggregation – A New Concept for Potential Treatment/Prevention of Alzheimers Disease
We have developed ligands that stabilise the Aβ peptide in the native helical conformation. These prevent Aβ induced reduction in hippocampal γ-oscillations (that is connected to cognition and learning and reduced in patients with AD) and oral administration of ligands increase longevity and decrease locomotor dysfunction in a Drosophila model of AD. As the approach holds promise for treatment of AD we are developing improved ligands.
Treatment of infections through substances that induce our own defence against microbes
Another goal is treatment of infections, in particular by multiresistant bacteria, through induction of body-own antimicrobial peptides. Developed inducers give increased levels of antimicrobial peptides both in the intestine and respiratory tract. Treated animals get complete recovery from shigellosis and a clinical trial for treatment of TB has been initiated.
Confocal microscopy of U2OS-cells treated with fluorescein-labeled (green colour), non-modified ONs (left panel) or with CPO-modified ONs (right panel).