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Synthesis of Lipid building blocks for therapeutic DNA/RNAs

Vejleder: Stefan Vogel

Forudsætninger: KE505 og KE506 skal være bestået.

Projektbeskrivelse

Introduction: The major obstacle to harvest the enormous potential of bioactive oligonucleotides is their delivery. The non-viral delivery of therapeutic oligonucleotides in low toxicity formulations is a currently unmet need. [1-2] In addition to the general delivery aspect, we aim to further developed our lipid membrane anchoring strategy for oligonucleotides to allow user friendly multiplexed formulation of lipidated oligonucleotides (LiNAs). [3-4]

Synthesis of lipid building blocks for incorporation into DNA/RNA 

Figure 1. Synthesis of lipid building blocks for incorporation into DNA/RNA

Methods: We look forward to methods in organic synthesis such as chemoselective acylations, metal-organic reductions, asymmetric substitution patterns on chiral compounds with building blocks for automated DNA/RNA synthesis in mind. This project is designed for students interested to learn more organic synthetic chemistry with applications in classical and automated synthesis with focus on bioactive biologicals such as therapeutic oligonucleotides.

References:

[1] Z. Glass, M. Lee, Y. Li and Q. Xu, Engineering the delivery system for CRISPR-based Genome Editing, Trends in Biotechnology, 2018, 36, 2, 173-185. [2] C. A. Lino, J. C. Harper, J. P. Carney and J. A. Timlin, Delivering CRISPR: a review of the challenges and approaches, Drug Delivery, 2018, 25, 1, 1234–1257. [3] S. Cogoi, U. Jakobsen, E. B. Pedersen, S. Vogel & L. E. Xodo, Lipid-modified G4-decoy oligonucleotide anchored to nanoparticles: delivery and bioactivity in pancreatic cancer cells Sci. Rep. 2016, 6, 1-13. [4] A. Ferino, G. Miglietta, R. Picco, S. Vogel, J. Wengel and L. E. Xodo, MicroRNA Therapeutics: Design of single-stranded miR-216b mimics to target KRAS in pancreatic cancer cells. RNA Biology, 2018

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Sidst opdateret: 22.08.2024