Chemical control of phase separation in DNA solutions

Hauf, Samuel; Yokobayashi, Yohei

doi:10.1039/d2cc06901f

Cited by 4 publications

(2 citation statements)

References 32 publications

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“…A series of experiments [1][2][3][4][5][6][7][8] have established that low complexity repeat RNA sequences, such as (CAG) n and (CUG) n , (n is the number of repeat units) undergo phase separation. In the two phase region, the high density droplet coexists with the sol or low density dispersed phase.…”

Section: Introductionmentioning

confidence: 99%

Salt-dependent self-association of trinucleotide repeat RNA sequences

Maity,

Nguyen,

Hori

et al. 2023

Preprint

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Low complexity repeat RNA sequences self-associate by homotypic interactions to form condensates. Using simulations of a coarse grained Single-Interaction Site model for (CAG)n(n= 30 and 31), we show that the salt-dependent free energy gap, ∆GS, between the ground (perfect hairpin) and the excited state (slipped hairpin (SH) with one CAG overhang) of monomer (neven) is the primary factor that determines the rates and yield of self-assembly. For oddn, the SH ground state free energy (GS) is used to predict self-association kinetics. As the monovalent salt concentration,CS, increases ∆GSandGSincreases, which in turn decreases the self-association rates. In contrast, ∆GSfor scrambled sequences, with the same length and sequence composition as (CAG)31but with higher complexity, is larger which greatly suppresses the propensities to aggregate. Although demonstrated explicitly for (CAG)30and (CAG)31polymers, the finding that there is an inverse correlation betweenCS-dependent ∆GSorGSand RNA aggregation is general. Our predictions are amenable to experimental tests.

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Section: Introductionmentioning

confidence: 99%

Salt-dependent self-association of trinucleotide repeat RNA sequences

Maity,

Nguyen,

Hori

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…A series of experiments − have established that low-complexity repeat RNA sequences, such as (CAG) n and (CUG) n (where n is the number of repeat units), undergo phase separation. In the two phase region, the high-density droplet coexists with the sol or low-density dispersed phase.…”

mentioning

confidence: 99%

Salt-Dependent Self-Association of Trinucleotide Repeat RNA Sequences

Maity,

Nguyen,

Hori

et al. 2024

J. Phys. Chem. Lett.

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Repeat RNA sequences self-associate to form condensates. Simulations of a coarse-grained single-interaction site model for (CAG) n (n = 30 and 31) show that the salt-dependent free energy gap, ΔG S , between the ground (perfect hairpin) and the excited state (slipped hairpin (SH) with one CAG overhang) of the monomer for (n even) is the primary factor that determines the rates and yield of self-assembly. For odd n, the free energy (G S ) of the ground state, which is an SH, is used to predict the self-association kinetics. As the monovalent salt concentration, C S , increases, ΔG S and G S increase, which decreases the rates of dimer formation. In contrast, ΔG S for shuffled sequences, with the same length and sequence composition as (CAG) 31 , is larger, which suppresses their propensities to aggregate. Although demonstrated explicitly for (CAG) polymers, the finding of inverse correlation between the free energy gap and RNA aggregation is general.

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Metal Ion-Condensed DNA Nanoparticle Library: Phase Separation and Transition and Antisense Therapy Applications

Moon,

Kim,

Lee

2024

ACS Appl. Mater. Interfaces

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DNA condensation has long been investigated as a fundamental cellular activity and is known to be driven by the mediation of diverse condensing agents. The phase behaviors of DNA during condensation are particularly interesting because the complicated molecular structure of natural nucleotides fundamentally allows electrostatic, coordinate covalent, and various other secondary interactions with the condensing agents. Recently, metal ion (M n+ )induced DNA condensation has emerged as a powerful approach to synthesizing nanoparticulate DNA structures suitable for therapeutic gene delivery. However, how the DNA phase changes during M n+induced DNA condensation has rarely been observed and is not understood yet. In this study, a library of M n+ -condensed DNA nanoparticles (M n+ -CDNPs) was established using 30 different types of M n+ s, and their phase behaviors during condensation were elucidated using spherical nucleic acids (SNAs) as electron microscopic labels. Importantly, the phase transition and separation of DNA were demonstrated to be driven by the M n+ s into either the growth of individual DNA particles or the fission of bulky DNA aggregates. Pt 2+ and Eu 3+ were chosen as model systems for the demonstration. The hard and soft acid nature of M n+ is presumably the underlying driving force of these phase transitions. In addition, the M n+ -controlled anticancer therapeutic efficiency of the M n+ -CDNP library as a state-of-the-art gene delivery platform was demonstrated even for unmodified antisense oligonucleotides in association with the potential toxicity of the M n+ s released from the M n+ -CDNPs. This comprehensive study of the M n+ -dependent condensation of nucleic acids provides profound insights into the chemistry of the nucleic acid−M n+ interactions and the reliable theragnostic applications of M n+ -CDNPs as functional nucleic acid nanostructures.

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Chemical control of phase separation in DNA solutions

Abstract: We designed a series of DNA sequences comprising a trinucleotide repeat segment and a small molecule-binding aptamer. Optimization of the DNA sequences and reaction conditions enabled chemical control of phase...

Cited by 4 publications

References 32 publications

Salt-dependent self-association of trinucleotide repeat RNA sequences

Salt-dependent self-association of trinucleotide repeat RNA sequences

Salt-Dependent Self-Association of Trinucleotide Repeat RNA Sequences

Metal Ion-Condensed DNA Nanoparticle Library: Phase Separation and Transition and Antisense Therapy Applications

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