Sequence Multiplicity within Spherical Nucleic Acids
| Autor: | Ziyin Huang, Shuya Wang, Chad A. Mirkin, Lisa E. Cole, Cassandra E. Callmann |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Cell signaling
Surface Properties Cell Oligonucleotides General Physics and Astronomy Sequence (biology) 02 engineering and technology 010402 general chemistry 01 natural sciences Article Cell Line Mice Nucleic Acids DNA nanotechnology medicine Animals General Materials Science Particle Size Oligonucleotide Chemistry General Engineering 021001 nanoscience & nanotechnology 0104 chemical sciences Mice Inbred C57BL medicine.anatomical_structure CpG site Nucleic acid Biophysics Signal transduction 0210 nano-technology |
| Zdroj: | ACS Nano. 14:1084-1092 |
| ISSN: | 1936-086X 1936-0851 |
| DOI: | 10.1021/acsnano.9b08750 |
| Popis: | The synthesis and evaluation of spherical nucleic acids (SNAs) incorporating two physically and chemically distinct classes of oligonucleotides (ODNs) at programmed ratios are described. These SNAs are single entity agents that enter the same target cell at defined stoichiometries, and as such allow one to control important cell signaling and regulatory processes. To study the effect of sequence multiplicity within such structures, we synthesized SNAs consisting of a mixture of class A CpG and class B CpG, immunostimulatory ODNs that activate two different toll-like receptor 9 signaling pathways, each in a sequence-specific fashion. These dual-CpG SNAs exhibit high cellular uptake and codelivery of the two ODNs, relative to mixtures of the linear ODN counterparts, and remain highly associated inside the cell over time. Furthermore, the dual-CpG SNAs augment dendritic cell maturation, compared to the same amounts of oligonucleotides delivered in linear or SNA form but not conjugated to one another. Consequently, these structures constitute a platform for designing oligonucleotide-based combination therapeutics with highly tailorable activities. |
| Databáze: | OpenAIRE |
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