PhD Position in Structure of siRNA/ASO's in Pharmaceutical Formulations

A PhD position within formulation of oligonucleotide based therapeutics is available at the Department of Physics, Chemistry, and Pharmacy in the pharmacy research group.

Starting date: 1 September 2022 or as soon as possible thereafter.

Project background
Compared to traditional small molecules, oligonucleotides (ONTs) have the advantage that their molecular target is defined by their sequence, making them highly specific and able to reach drug targets impossib le to af fect otherwise. Therapeutic ONTs comprise a variety of molecular classes, including antisense ONT (ASOs), small interfering RNAs (siRNAs), and aptamers. More than 280 clinical trials are ongoing with ONTs with different indications. The huge potential of ONTs is yet to be fulfilled as issues with their delivery have so far hampered their clinical use.

Through non-covalent interactions (H-bonding, p-p stacking, etc.), an ONT can adopt different higher-order structures (HOS), such as single and double strands, hairpin loops, cruciforms, triplexes, quadruplexes. The sequence highly defines the HOS, but also environmental conditions contribute to the (de)stabilization of the ONT HOS. Irrespective of the mechanism of action, pharmaceutical ONTs must adopt a specific HOS when they reach their target . There is a strong structure-activity relationship for ONTs - they will not bind their target if not in their designed conformation. As the formulation composition has an activ e and critical role on the (de)stabilization of HOS and on potential transitions between different conformations, this PhD work will investigate these elements deeper.

Qualifications
We are looking for a candidate with a strong interest in working on the boundary between pharmacy and chemistry focused on formulation design for ONTs and analytical characterisation of what this may do to the drug molecule during and after manufacturing of the formulations. The candidate will hold an MSc in pharmacy, chemistry, physics, or a closely related area. Previous experiences with one or more of the following is considered an advantage: formulation design of liposomes, lipid nanopartciles or similar, circular dichroism and other relevant analytical techniques.

The candidate must be independent and fluent in both oral and written English.

Deadline: 1 August 2022.

Please see the full call, including how to apply, on www.sdu.dk .