2 Citations
Nucleic acid nanoparticles NANPs fabricated by using the DNA origami method have broad utility in materials science and bioengineering Their site-specific heterovalent functionalization with secondary molecules such as proteins or fluorophores is a unique feature of this technology that drives its utility Currently however there are few chemistries that enable fast efficient covalent functionalization of NANPs with a broad conjugate scope and heterovalency To address this need we introduce synthetic methods to access inverse electron-demand Diels Alder chemistry on NANPs We demonstrate a broad conjugate scope characterize application-relevant kinetics and integrate this new chemistry with strain-promoted azide alkyne cycloaddition chemistry ... More
Nucleic acid nanoparticles (NANPs) fabricated by using the DNA origami method have broad utility in materials science and bioengineering. Their site-specific, heterovalent functionalization with secondary molecules such as proteins or fluorophores is a unique feature of this technology that drives its utility. Currently, however, there are few chemistries that enable fast, efficient covalent functionalization of NANPs with a broad conjugate scope and heterovalency. To address this need, we introduce synthetic methods to access inverse electron-demand Diels–Alder chemistry on NANPs. We demonstrate a broad conjugate scope, characterize application-relevant kinetics, and integrate this new chemistry with strain-promoted azide–alkyne cycloaddition chemistry to enable heterovalent click reactions on NANPs. We applied these chemistries to formulate a prototypical chemical countermeasure against chemical nerve agents. We envision this additional chemistry finding broad utility in the synthetic toolkit accessible to the nucleic acid nanotechnology community. Less
Nucleic acid nanoparticles NANPs are increasingly used in preclinical investigations as delivery vectors Tools that can characterize assembly and assess quality will accelerate their development and clinical translation Standard techniques used to characterize NANPs like gel electrophoresis lack the resolution for precise characterization Here we introduce the use of charge detection mass spectrometry CD-MS to characterize these materials Using this technique we determined the mass of NANPs varying in size shape and molecular mass NANPs varying in production quality due to formulations lacking component oligonucleotides and NANPs functionalized with protein and nucleic acid-based secondary molecules Based on these demonstrations CD-MS ... More
Nucleic acid nanoparticles (NANPs) are increasingly used in preclinical investigations as delivery vectors. Tools that can characterize assembly and assess quality will accelerate their development and clinical translation. Standard techniques used to characterize NANPs, like gel electrophoresis, lack the resolution for precise characterization. Here, we introduce the use of charge detection mass spectrometry (CD-MS) to characterize these materials. Using this technique, we determined the mass of NANPs varying in size, shape, and molecular mass, NANPs varying in production quality due to formulations lacking component oligonucleotides, and NANPs functionalized with protein and nucleic acid-based secondary molecules. Based on these demonstrations, CD-MS is a promising tool to precisely characterize NANPs, enabling more precise assessments of the manufacturing and processing of these materials. Less