PhD Position on Designing of Novel Lipid-Based Targeting Ligands for Enhanced Oligonucleotide Delivery

Contract @AstraZeneca R&D in Life Sciences
  • Sweden, Pepparedsleden 1, 431 83 Mölndal, Sweden View on Map
  • Post Date : January 30, 2025
  • Apply Before : March 15, 2025
  • View(s) 79

Job Detail

  • Job ID 94200
  • Qualifications  Master’s Degree

Job Description

As part of the European EFFecT Consortium, the Oligonucleotide Chemistry and Targeted Delivery Team at AstraZeneca R&D Gothenburg in Sweden is seeking for a passionate PhD student interested in developing and applying novel chemistries to expand the use of Oligonucleotide Therapeutics. If you are interested to apply, please visit: https://lnkd.in/dfj3KBUd

Job description:

Supervisor: Prof.  S. Andersson (Shalini.Andersson@astrazeneca.com) and Dr. A. Biscans (annabelle.biscans@astrazeneca.com)
Host Institute: AstraZeneca, Gothenburg (www.astrazeneca.com)

Secondments planned: Radboud University Medical Center, The Netherlands; Karolinksa Institute, Sweden

Doctoral program: PhD program of Karolinska Institute

How to apply: Submit a single pdf document as indicated in the section ‘How to apply’ to lonneke.duijkers@radboudumc.nl

Anticipated starting date: September 1st, 2025

Project description DC6@AZ:

Oligonucleotide therapeutics, such as antisense oligonucleotides (ASOs) and small interfering RNA (siRNA), are emerging medicines to treat diseases with unmet medical needs. However, they are highly anionic large molecules, preventing them from penetrating cell membranes via passive diffusion like small molecule drugs. Therefore, to use oligonucleotides as medicines, strategies to improve their cellular uptake and delivery to specific tissues are needed. Direct conjugation of oligonucleotides with ligands has shown great promise in efficiently delivering oligonucleotides. While GalNAc ligands have proven effective for delivering oligonucleotides to the liver, leading to several clinical candidate drugs, the development of ligands capable of targeting other organs has seen limited success. This project aims to address this delivery challenge by designing various lipid-based targeting ligands for efficient delivery of oligonucleotides to cardiac tissue. Diverse lipid-based siRNA conjugates will be synthesized and evaluated in vitro to assess their cellular uptake, efficiency, and toxicity. Promising candidates will be further assessed in relevant cardiac cell lines and in vivo in rodent models to gain insights into translational aspects, pharmacokinetics/pharmacodynamics (PK/PD), and duration of action. Additionally, we aim to map how lipid structure impacts the biodistribution of oligonucleotides and influences the therapeutic window. DC6 will have the opportunity to collaborate with biologists to evaluate the most promising lipid conjugates in relevant disease models.

Profile of the candidate:

We are seeking a highly motivated candidate with scientific curiosity, ambition to succeed, and a results-oriented mindset. The ideal candidate should have:

  • A Master’s degree (MSc) in Organic Chemistry.
  • A solid theoretical background in organic synthesis.
  • Hands-on experience with multistep organic synthesis, compound purification, and characterization techniques.
  • Experience with oligonucleotide therapeutics is a plus but not required.
  • Excellent communication skills in English, both spoken and written, are essential.

The candidate should be strongly motivated and capable of operating effectively in a multidisciplinary research environment.

 

Required skills

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