Sprecher
Beschreibung
Membraneless organelles, such as DNA/RNA condensates formed via liquid-liquid phase separation (LLPS), provide a flexible and dynamic platform for biosensing applications in therapeutic advancements.1, 2 The DNA condensates may offer a biomimetic environment for molecular recognition, enabling the detection of disease biomarkers with high sensitivity and specificity. By leveraging multivalent interactions, DNA condensates can be engineered to respond to specific nucleic acid sequences, proteins, or small molecules, making them ideal for sensing and targeted drug delivery.1-3 The condensates also play a crucial role in regulating intracellular machinery and maintaining physiological homeostasis in biological system.2, 4 In the context of cancer, DNA condensate-based biosensors may facilitate real-time monitoring of disease progression and therapeutic response. Additionally, their tunable physicochemical properties may allow for controlled drug release, improving therapeutic efficacy while minimizing off-target effects.2-5
Here, we aim to develop nucleic acid condensate as a biosensing and delivery platform of therapeutic for cancer and other critical diseases. We employ circular dichroism (CD) spectroscopy as a label-free technique to detect DNA condensates and explore potential of condensates as delivery platform for therapeutic oligonucleotides. DNA Y-stem nanostars were used to generate DNA-based droplets, which could serve as delivery vehicles for therapeutic oligonucleotides such as anti-miRNA21. Time-dependent CD and fluorescence imaging confirmed formation and growth of condensate over time. The oligonucleotide anti-miRNA21 were observed to be compartmentalized in phase separated droplets via functionalization with Zipped Nucleic Acid (ZNA) as revealed using fluorescence imaging. As a next step, DNA droplets loaded with therapeutic are intended for delivery into cellular systems to evaluate their real-time cargo release potential on target sites, contributing to the development of advanced therapeutic strategies. This work could open a new avenue for targeted delivery of therapeutics in the new era of personalized medicine.
