Synthesis of modified oligonucleotides for the improvement of DNA origami cellular uptake


Haasnoot Martí, Pablo


Nucleic acids and their biomedical applications have been for a long period of time underrated by the scientific community when compared to the more classical and studied peptides. It was not until the 20th century that nucleic acid therapies and molecules started to surface, mainly thanks to the advances on the optimization of the synthesis of oligonucleotides. DNA nanostructures are some of the more complex DNA based molecules that are still in a developmental stage, but yet already show huge potential as biomarkers, and/or for industrial and biomedical purposes. DNA origami is one of such nanostructures that is being extensively studied and has seen some great improvement in the recent decades. This nanostructure is created by exploiting the base pairing system described by Watson and Crick, using short oligonucleotide sequences which show complementary for different places of a larger single strand of DNA. This way it is possible to reach non-conventional DNA structures which are more stable inside the blood stream in combination of the advantageous properties nucleic acid have as carrier devices. Nevertheless, DNA nanostructures still face multiple challenges to overcome such as its abundant negative charge. We suggested the combination of simple fatty acid (FA) molecules and folic acid as potential enhancers of DNA origami’s cellular uptake. In the project below, we demonstrate two different pathways for the synthesis of oligonucleotide – lipid conjugates that do not interfere on DNA origami formation and that reach and increased level of cell internalization. The results shown in this work suggest that addition of lipidic compounds into DNA nanostructures might be enough to enhance the good internalization rate, leaving the more commonly used complex lipidic particles outdated as drug delivery systems for biomedical applications.



Planas Sauter, Antoni
Eritja, Ramon


IQS SE - Undergraduate Program in Biotechnology