SUMMARY
The Bujold group’s principal research interests reside in oligonucleotide chemistry, DNA self-assembly, chemical biology and drug delivery. Our research group focuses on the synthesis of chemically modified oligonucleotides and nucleic acids nanostructures to modulate their interactions with living systems for applications in precision medicine. Towards this, we use a toolset focusing on:
Oligonucleotide Chemistry
Development of automated synthesis protocols for cationic oligonucleotides, synthesis of oligonucleotides with controlled charge, development of self-transfecting oligonucleotides and assemblies.
DNA Nanotechnology
Creation of well-defined nucleic acid-based nanostructures for biological applications, development of stimuli-responsive nanostructures, DNA nanostructures for the encapsulation, and selective release of biomolecule drugs.
Bioconjugation
Conjugation of oligonucleotides onto gold nanoparticles and proteins to form spherical nucleic acids, incorporation of click chemistry handles and other reactive groups to form peptide and glycan conjugates, as well as radiolabeled functional oligonucleotides and nanoscale assemblies.
Nucleic Acid Therapeutics
Drug delivery scaffolds for nucleic acid therapeutics, incorporation of modified nucleosides within nucleic acid therapeutics, delivery, and potency assessment in cell models.
Chemical Biology
Precise biomolecule assemblies and chemical tools to address biological questions (e.g., drug delivery with biomolecules, interfacing with cells), incorporation of fluorophores and radiolabels to track oligonucleotide location and function in living systems.
PROJECTS
Chemically modified nucleic acid
nanostructures to improve cellular uptake
Unmodified nucleic acids typically show poor cellular uptake, which is a challenge as they are translated to the clinic. We are exploring chemical modifications and their placement at the nanoscale to enable them to access different uptake mechanisms and improve their functionality in cells, which will provide alternative uptake pathways for nucleic acids. Cationic oligonucleotide modifications are particularly attractive in this context to due to their ability to facilitate uptake, which we are assessing to improve localization and function of nucleic acid drugs. Click here to watch our video on: Development of Nucleic Acid-Based Nanostructures for Applications at the Interface with Biology
Oligonucleotide conjugates for cell-specific
targeting and immune activation
Arginine-rich cell-penetrating peptides (CPPs) have been thoroughly investigated since the discovery that the Tat peptide can promote cell entry for an entire virus. Peptides have since been reported, which bind cell components, such as glycosaminoglycans (GAGs), and can transport cargo into cells. We are developing DNA-peptide conjugates and nanostructures that precisely position GAG-binding peptides with programmed geometries to achieve selective cell entry based on GAG expression patterns. Click here to watch our video on how Oligonucleotides are made:
