Synthetic Biology
DNA decoy-based targeted therapeutics for autoimmune diseases using dynamic DNA nanotechnology
Autoimmune diseases arise when the immune system, designed to protect the body from foreign invaders such as pathogens and infections, erroneously targets and attacks the body’s healthy cells and tissues. This misdirection can result in a wide array of health issues, including rheumatoid arthritis, lupus, multiple sclerosis, and type 1 diabetes. To address the challenges posed by autoimmune diseases, our research leverages the programmable nature of synthetic DNA oligonucleotides and aptamers, enabling the design of DNA circuits that convert biological signals into distinct molecular responses.
By designing and constructing sophisticated DNA-based therapeutic agents, we can create systems that selectively identify and interact with specific biomarkers associated with various autoimmune conditions. For instance, in cases where the immune system is overactive and attacks healthy tissue, these agents can help re-establish a more balanced immune response, reducing inflammation and tissue damage and thus allowing for precise modulation of immune responses.
Designing Transcription factor (TF) decoys for regulating gene expression
TF decoys are short ds DNA sequences that can act like a sponge to soak up free transcription factors in the cell and divert them from their native binding site. This can be harnessed to alter the protein expression and regulate immunological pathways. However, transfecting unmodified transcription factors (TFs) into cells is challenging because the negative charge of DNA causes repulsion at the cell membrane. Additionally, if they do enter, these oligonucleotides are rapidly degraded by nucleases and other enzymes within the cell. This issue can be solved by using DNA-based nanostructures. DNA can fold into different polyhedra due to its flexible nature and the turns of double-stranded DNA, which are also quite stable in the cellular environment, unlike double-stranded DNA-based circuits.
We are currently focused on building a DNA-based Tetrahedron that can mimic transcription factor binding sites, functioning as a decoy that can bind to transcription factors and regulate gene expression. We are currently testing the transfection and interaction of the TF decoy in E coli, which binds to the Lac repressor, and can regulate GFP expression.
Applications of toehold mediated strand displacement reaction for biomedical applications
Dynamic DNA nanotechnology is applied in several biomedical applications, including biosensing for rapid pathogen detection and SNP sensing for personalized medicine. Additionally, these DNA constructs are utilized in therapeutics for controlled drug delivery, achieved by integrating DNA circuits with hydrogels to facilitate targeted drug release. This research aims to enhance the functionality of synthetic DNA in diagnostics and therapeutics, enabling innovative strategies to address significant health challenges.