Oligomer Duplexes Research Articles

Comparison qPCR study for selecting a valid single copy gene for measuring absolute telomere length

Telomere shortening is a well-known biomarker for biological aging. A previous review of the methods used to measure telomere length (TL) noted how challenging it is to compare results from different studies using diverse methodological techniques. The most commonly used high throughput method for measuring average TL is the quantitative PCR (qPCR) method, where there are two protocols available; the relative TL and the absolute TL (aTL) method. All qPCR methods have similarities in that they use two different primer sets to measure the telomere repeat sequence (TTAGGG)n and a single copy gene region to calculate the average TL, (T/S) ratio. The difference between the relative TL and the aTL assay lies with the introduction of duplex oligomer standards to identify TL in kilobase pairs rather than using the traditional relative TL, T/S ratio method. Problems were noted using 36B4 (RPLP0), which was originally used as a suitable single copy gene qPCR assay. A previous aTL publication attempted to replace the 36B4 (RPLP0) single copy gene using the Interferon beta 1 gene (IFNB1) but results showed a lack of agreement with the TL results when compared to the DNAmTL assay. Here, we compare the two single copy gene assays previously used for the aTL assay and offer an alternative IFNB1 single copy gene assay without non-specific priming amplification to provide more consistent diploid copy number determination and a more robust and reproducible assay for measuring absolute TL.

Single Stranded Fully Modified-Phosphorothioate Oligonucleotides can Induce Structured Nuclear Inclusions, Alter Nuclear Protein Localization and Disturb the Transcriptome In Vitro.

Oligonucleotides and nucleic acid analogues that alter gene expression are now showing therapeutic promise in human disease. Whilst the modification of synthetic nucleic acids to protect against nuclease degradation and to influence drug function is common practice, such modifications may also confer unexpected physicochemical and biological properties. Gapmer mixed-modified and DNA oligonucleotides on a phosphorothioate backbone can bind non-specifically to intracellular proteins to form a variety of toxic inclusions, driven by the phosphorothioate linkages, but also influenced by the oligonucleotide sequence. Recently, the non-antisense or other off-target effects of 2′ O- fully modified phosphorothioate linkage oligonucleotides are becoming better understood. Here, we report chemistry-specific effects of oligonucleotides composed of modified or unmodified bases, with phosphorothioate linkages, on subnuclear organelles and show altered distribution of nuclear proteins, the appearance of highly stable and strikingly structured nuclear inclusions, and disturbed RNA processing in primary human fibroblasts and other cultured cells. Phosphodiester, phosphorodiamidate morpholino oligomers, and annealed complimentary phosphorothioate oligomer duplexes elicited no such consequences. Disruption of subnuclear structures and proteins elicit severe phenotypic disturbances, revealed by transcriptomic analysis of transfected fibroblasts exhibiting such disruption. Our data add to the growing body of evidence of off-target effects of some phosphorothioate nucleic acid drugs in primary cells and suggest alternative approaches to mitigate these effects.

Structural insight into locked nucleic acid based novel antisense modifications: A DFT calculations at monomer and MD simulations at oligomer level

In the present study, five novel LNA based antisense modifications have been proposed. A conformational search was carried out using TANGO, followed by geometry optimization using MOPAC. Based on their electronic energies the most stable conformation for each modification was identified. Further, DFT based full geometry optimization on the most stable conformations at the gas phase B3LYP/6-31G(d,p) using a Gaussian03 and single point energy calculations on the optimized structures at the solvent phase B3LYP/6-311G(d,p) level of theory were done to derive their quantum chemical descriptors using the Gaussian09. A comparison of global reactivity descriptors confirmed that the LNA based modifications were the most reactive. Base-pair stability was recorded by observing the binding energies and base-pairing conformations of modified GC base pairs at the B3LYP/6-311G(d,p) level of theory. Molecular dynamics simulations have been performed at the oligomer duplex level by incorporating individual modifications on 20-mer RNA-RNA duplexes using AMBER16. Free energy calculations of duplex structures suggested that incorporation of A2 modification into the RNA-RNA duplex increased the duplex binding affinity similar to LNA. Whereas, the A3 modification showed less binding compared to LNA but improved binding compared to MOE. This computational approach using quantum chemical methods may be very useful to propose better modifications than the existing ones before performing the experiments in the area of antisense technology.

Elasticity and Viscosity of DNA Liquid Crystals.

Concentrated solutions of blunt-ended DNA oligomer duplexes self-assemble in living polymers and order into lyotropic nematic liquid crystal phase. Using the optical torque provided by three distinct illumination geometries, we induce independent splay, twist, and bend deformations of the DNA nematic and measure the corresponding elastic coefficients K1, K2, and K3, and viscosities ηsplay, ηtwist, and ηbend. We find the viscoelasticity of the system to be remarkably soft, as the viscoelastic coefficients are smaller than in other lyotropic liquid crystals. We find K1 > K3 > K2, in agreement with the elasticity of the nematic phase of flexible polymers, and ηbend > ηsplay > ηtwist a behavior that is nonconventional in the context of chromonic, polymeric, and thermotropic liquid crystals, indicating a possible role of the weakness and reversibility of the DNA aggregates.

The DNA conformational energy landscape: sequence-dependent conformational equilibria of duplex DNA

The free energy surfaces of duplex dinucleotide steps were mapped in a principal conformational subspace derived from crystal structure data on DNA duplex oligomers. The three dimensional subspace, spanned by collective degrees of freedom representing linear combinations of the Cartesian coordinates of the backbone and sugar atoms of both strands accounted for 77% of the total variance of the observed structural distribution. The features of the subspace free energy surface correspond well to the distribution of observed structures exhibiting a clear separation of A- and B-family classes. The sequence dependence of the relative A / B-form conformational equilibria was derived from the corresponding subspace free energy surfaces at physiological conditions. A B-philicity scale representing the mole fraction of the BI-form vs the A-family for the 10 unique dinucleotide steps revealed three classes of sequences: highly B-philic (GC/GC & CG/CG), B-philic (AC/GT, AA/TT, AT/AT, CA/TG, AG/CT & GG/CC) and A-philic (GA/TC & TA/TA). The high propensity of the TA/TA step to adopt the A-form conformation is in accord with single crystal X-ray diffraction data and has biological significance in view of the frequent presence of the TATA sequence motif in transcriptional promoter regions.

Structural insight into antisense gapmer-RNA oligomer duplexes through molecular dynamics simulations

There is an extensive research carrying out on antisense technology and the molecules entering into clinical trials are increasing rapidly. Phosphorothioate (PS) is a chemical modification in which nonbridged oxygen is replaced with a sulfur, consequently providing resistance against nuclease activity. The 2'-4' conformationally restricted nucleoside has the structural features of both 2'-O-methoxy ethyl RNA (MOE), which shows good toxicity profile, and locked nucleic acid (LNA), which shows good binding affinity towards the target RNA. These modifications have been studied and suggested that they can be a potential therapeutic agents in antisense therapy. Mipomersen (ISIS 301012), which contains the novel nucleoside modification has been used to target to apolipoprotein (Apo B), which reduces LDL cholesterol by 6–41%. In this study, classical molecular dynamics (MD) simulations were performed on six different antisense gapmer/target-RNA oligomer duplexes (LNA-PS-LNA/RNA, RcMOE-PS-RcMOE/RNA, ScMOE-PS-ScMOE/RNA, MOE-PS-MOE/RNA, PS-DNA/RNA and DNA/RNA) to investigate the structural dynamics, stability and solvation properties. The LNA, MOE nucleotides present in respective duplexes are showing the structure of A-form and the PS-DNA nucleotides resemble the structure of B-form helix with respect to some of the helical parameters. Free energy calculations suggest that the oligomer, which contains LNA binds to the RNA strongly than other modifications as shown in experimental results. The MOE modified nucleotide, which although had a lower binding affinity but higher solvent accessible surface area (SASA) compared to the other modifications, may be influencing the toxicity and hence may be used it in Mipomersen, the second antisense molecule which is approved by FDA.Communicated by Ramaswamy H. Sarma

The crystal structure of Z-DNA with untypically coordinated Ca2+ ions.

DNA oligomer duplexes with alternating cytosines and guanines in their sequence tend to form helices of the Z-DNA type, where the sugar and phosphate backbone forms a left-handed helix in a zigzag fashion with a repeat of two successive Watson-Crick pairs of nucleotides. Z-DNA duplexes often crystallize in complexes with diverse metal ions interacting with polar DNA atoms in various ways. This work describes the high-resolution crystal structure of a Z-DNA d(CGCGCG)2 duplex in complex with Ca2+ ions, unusually coordinated as an approximate pentagonal bipyramid by two neighboring guanines through their O6 and N7 atoms and a water molecule in the equatorial plane and a phosphate oxygen atom and another water molecule in the apical positions.

Four highly pseudosymmetric and/or twinned structures of d(CGCGCG)2extend the repertoire of crystal structures of Z-DNA

DNA oligomer duplexes containing alternating cytosines and guanines in their sequences tend to form left-handed helices of the Z-DNA type, with the sugar and phosphate backbone in a zigzag conformation and a helical repeat of two successive nucleotides. Z-DNA duplexes usually crystallize as hexagonally arranged parallel helical tubes, with various relative orientations and translation of neighboring duplexes. Four novel high-resolution crystal structures of d(CGCGCG)2 duplexes are described here. They are characterized by a high degree of pseudosymmetry and/or twinning, with three or four independent duplexes differently oriented in a monoclinic P21 lattice of hexagonal metric. The various twinning criteria give somewhat conflicting indications in these complicated cases of crystal pathology. The details of molecular packing in these crystal structures are compared with other known crystal forms of Z-DNA.

Application of differential scanning calorimetry to measure the differential binding of ions, water and protons in the unfolding of DNA molecules

BackgroundThe overall stability of DNA molecules globally depends on base-pair stacking, base-pairing, polyelectrolyte effect and hydration contributions. In order to understand how they carry out their biological roles, it is essential to have a complete physical description of how the folding of nucleic acids takes place, including their ion and water binding. Scope of reviewTo investigate the role of ions, water and protons in the stability and melting behavior of DNA structures, we report here an experimental approach i.e., mainly differential scanning calorimetry (DSC), to determine linking numbers: the differential binding of ions (Δnion), water (ΔnW) and protons (ΔnH+) in the helix–coil transition of DNA molecules. General significanceWe use DSC and temperature-dependent UV spectroscopic techniques to measure the differential binding of ions, water, and protons for the unfolding of a variety of DNA molecules: salmon testes DNA (ST-DNA), one dodecamer, one undecamer and one decamer duplexes, nine hairpin loops, and two triplexes. These methods can be applied to any conformational transition of a biomolecule. Major conclusionsWe determined complete thermodynamic profiles, including all three linking numbers, for the unfolding of each molecule. The favorable folding of a DNA helix results from a favorable enthalpy-unfavorable entropy compensation. DSC thermograms and UV melts as a function of salt, osmolyte and proton concentrations yielded releases of ions and water. Therefore, the favorable folding of each DNA molecule results from the formation of base-pair stacks and uptake of both counterions and water molecules. In addition, the triplex with C+GC base triplets yielded an uptake of protons. Furthermore, the folding of a DNA duplex is accompanied by a lower uptake of ions and a similar uptake of four water molecules as the DNA helix gets shorter. In addition, the oligomer duplexes and hairpin thermodynamic data suggest ion and water binding depends on the DNA sequence rather than DNA composition. This article is part of a Special Issue entitled Microcalorimetry in the BioSciences — Principles and Applications, edited by Fadi Bou-Abdallah.

A one-pot strategy for the sensitive detection of miRNA by catalyst–oligomer-mediated enzymatic amplification-based fluorescence biosensor

MiRNAs have become an ideal class of biomarker candidates for cancer classification, diagnosis, and prognosis. However, traditional approaches for the detection of miRNAs are usually laborious and time-consuming with a low sensitivity. We developed an ultrasensitive one-pot miRNA detection strategy that uses catalyst–oligomer-mediated enzymatic amplification (CMEA) sensor to circumvent the aforementioned limitations in miRNA detection. In this assay, we employed three oligonucleotides, DNA1, protector–oligomer, and catalyst–oligomer. One target miRNA can generation thousands of DNA1/catalyst–oligomer duplex. Since the DNA1/catalyst–oligomer duplex contains an endonuclease sites for Nt.CviPII, DNA1 can be cleaved into two pieces by this NEase, which leads to the denaturation of the DNA1/catalyst–oligomer duplex and thus results in a significant fluorescence signal intensity increase. Notably, this method can sensitively measure Let-7a with a detection limit of 10fM, which has improved by as much as 7 orders of magnitude higher than that of the photoinduced electron transfer (PET) method without any amplification. Importantly, this method can be used to measure Let-7a in A549 cell extracts and might be further applied for the detection of various miRNA.

Thermodynamics of Denaturation Transition of DNA Duplex Oligomers in the Context of Nearest Neighbor Models: A Short Review

In this article, it is shown how additive physical properties of DNA double strand polymers can be expanded in terms of 8 irreducible parameters. This provides self-consistency relations among the corresponding 10 duplex dimer contributions. To allow for oligomer analysis, initiation parameters must be added, and, this adds extra degrees of freedom to the fore mentioned parameters. This modelling permits that nucleation free energies could be calculated as a function of the mean global composition of the chain.

Processing of abasic site damaged lesions by APE1 enzyme on DNA adsorbed over normal and organomodified clay

The efficiency of the apurinic/apyrimidinic endonuclease (APE1) DNA repair enzyme in the processing of abasic site DNA damage lesions at precise location in DNA oligomer duplexes that are adsorbed on clay surfaces was evaluated. Three different forms of clay namely montmorillonite, quaternary ammonium salt modified montmorillonite and its boiled counterpart i.e. partially devoid of organic moiety were used for a comparative study of adsorption, desorption and DNA repair efficiency on their surfaces. The interaction between the DNA and the clay was analysed by X-ray diffraction, Atomic force microscopy, UV–Vis spectroscopy and Infrared spectroscopy. The abasic site cleavage efficiency of APE1 enzyme was quantitatively evaluated by polyacrylamide gel electrophoresis. Apart from the difference in the DNA adsorption or desorption capacity of the various forms of clay, substantial variation in the repair efficiency of abasic sites initiated by the APE1 enzyme on the clay surfaces was observed. The incision efficiency of APE1 enzyme at abasic sites was found to be greatly diminished, when the DNA was adsorbed over organomodified montmorillonite. The reduced repair activity indicates an important role of the pendant surfactant groups on the clay surfaces in directing APE1 mediated cleavage of abasic site DNA damage lesions.

Calculation of nucleation free energy for duplex oligomers in the context of nearest neighbor models

Additive physical properties of DNA double strand polymers have been expanded in terms of 8 irreducible parameters. This provided consistency relations among the corresponding 10 duplex dimer contributions. To allow for oligomer analysis, end parameters were often added, and this would add extra degrees of freedom to the fore mentioned parameters. Statistical mechanics approaches were then connected to the nearest neighbor (NN) approach in the framework of the two-states model. Ad hoc end effects were thus (wrongly) correlated to nucleation phenomena and this lead to a critique for its role in NN modeling. With this motivation, a new NN model is proposed that accommodates the nucleation free energies. The model relates the nucleation free energy to the mean composition of the chain and permits to obtain a good estimate for the free energy associated only to the Watson-Crick base pairings.

Condensation of DNA—A putative obstruction for repair process in abasic clustered DNA damage

Clustered DNA damages are defined as two or more closely located DNA damage lesions that may be present within a few helical turns of the DNA double strand. These damages are potential signatures of ionizing radiation and are often found to be repair resistant. Types of damaged lesions frequently found inside clustered DNA damage sites include oxidized bases, abasic sites, nucleotide dimers, strand breaks or their complex combinations. In this study, we used a bistranded two-lesion abasic cluster DNA damage model to access the repair process of DNA in condensate form.Oligomer DNA duplexes (47bp) were designed to have two deoxyuridine in the middle of the sequences, three bases apart in opposite strands. The deoxyuridine residues were converted into abasic sites by treatment with UDG enzyme creating an abasic clustered damage site in a precise position in each of the single strand of the DNA duplex. This oligomer duplex having compatible cohesive ends was ligated to pUC19 plasmid, linearized with HindIII restriction endonuclease. The plasmid–oligomer conjugate was transformed into condensates by treating them with spermidine. The efficiency of strand cleavage action of ApeI enzyme on the abasic sites was determined by denaturing PAGE after timed incubation of the oligomer duplex and the oligomer–plasmid conjugate in presence and absence of spermidine. The efficiency of double strand breaks was determined similarly by native PAGE. Quantitative gel analysis revealed that rate of abasic site cleavage is reduced in the DNA condensates as compared to the oligomer DNA duplex or the linear ligated oligomer–plasmid conjugates. Generation of double strand break is significantly reduced also, suggesting that their creation is not proportionate to the number of abasic sites cleaved in the condensate model. All these suggest that the ApeI enzyme have difficulty to access the abasic sites located deep into the condensates leading to repair refractivity of the damages. In addition, we found that presence of a polyamine such as spermidine has no notable effect in the incision activity of ApeI enzyme in linear oligomer DNA duplexes in our experimental concentration.

Oligomer Duplex Tearing and Shearing Mechanisms in the Nanopore

The nanopore has been developed as a molecule force microscope to explore the dissociation of oligomer duplex, such as the double-stranded DNA/RNA and hairpin duplexes, or DNA-RNA hybrids. The oligomer duplexes can be trapped in the nanopore can generate long current blocks. By measuring the voltage-dependent block duration, the unzipping kinetics as well as the force and energy involved in the double strands hybridization can be characterized. However, few studies have presented convincing characteristic current patterns for the dissociation occurrence. In this report, we uncovered signature current patterns that can electrically track the dissociation processes in tear and shear geometry, from the time course of dissociation to the motion pathway of the unzipped single-stranded DNA. With the signature signals, the duplex trapping-unzipping, and trapping-escaping without unzipping as well as trapping directionality can also be distinguished. Quantitative analysis of signature signals showed that the oligomer duplex with a single-stranded overhang is more easily to be trapped in the nanopore compared to the blunt-ended duplex. Therefore the overhang is not only an unzipping driver, but also a controller of DNA trapping orientation, regulating the duplex dissociation in a programmable manner. Discrimination of duplex dissociation signatures not only gives precise insight into the dissociation mechanisms, but more importantly in biosensors for detection of disease-related biomarkers. These dissociation signatures can serve as a single-molecule elecrical marker that ensures both selectivity and sensitivity.

Stability and Mismatch Discrimination of Locked Nucleic Acid–DNA Duplexes

Locked nucleic acids (LNA; symbols of bases, +A, +C, +G, and +T) are introduced into chemically synthesized oligonucleotides to increase duplex stability and specificity. To understand these effects, we have determined thermodynamic parameters of consecutive LNA nucleotides. We present guidelines for the design of LNA oligonucleotides and introduce free online software that predicts the stability of any LNA duplex oligomer. Thermodynamic analysis shows that the single strand–duplex transition is characterized by a favorable enthalpic change and by an unfavorable loss of entropy. A single LNA modification confines the local conformation of nucleotides, causing a smaller, less unfavorable entropic loss when the single strand is restricted to the rigid duplex structure. Additional LNAs adjacent to the initial modification appear to enhance stacking and H-bonding interactions because they increase the enthalpic contributions to duplex stabilization. New nearest-neighbor parameters correctly forecast the positive and negative effects of LNAs on mismatch discrimination. Specificity is enhanced in a majority of sequences and is dependent on mismatch type and adjacent base pairs; the largest discriminatory boost occurs for the central +C·C mismatch within the +T+C+C sequence and the +A·G mismatch within the +T+A+G sequence. LNAs do not affect specificity in some sequences and even impair it for many +G·T and +C·A mismatches. The level of mismatch discrimination decreases the most for the central +G·T mismatch within the +G+G+C sequence and the +C·A mismatch within the +G+C+G sequence. We hypothesize that these discrimination changes are not unique features of LNAs but originate from the shift of the duplex conformation from B-form to A-form.

Synthesis of Complementary Double-Stranded Helical Oligomers through Chiral and Achiral Amidinium−Carboxylate Salt Bridges and Chiral Amplification in Their Double-Helix Formation

A series of complementary molecular strands from 2-mer to 5-mer that are composed of m-terphenyl units bearing chiral/achiral amidine or achiral carboxyl groups linked via Pt(II) acetylide complexes were synthesized by sequential stepwise reactions, and their chiroptical properties on the double-helix formation were investigated by circular dichroism (CD) and (1)H NMR spectroscopies. In CHCl(3), the "all-chiral" amidine strands consisting of (R)- or (S)-amidine units formed preferred-handed double helices with the complementary achiral carboxylic acid strands through the amidinium-carboxylate salt bridges, resulting in characteristic induced CDs in the Pt(II) acetylide complex regions, indicating that the chiral substituents on the amidine units biased a helical sense preference. The Cotton effect patterns and intensities were highly dependent on the molecular lengths. The complementary double-helix formation was also explored using the chiral/achiral amidine strands with different sequences in which a chiral amidine unit was introduced at the center (center-chiral) or a terminus (edge-chiral) of the amidine strands. The effect of the sequences of the chiral and achiral amidine units on the amplification of chirality (the "sergeants and soldiers" effect) in the double-helix formation was investigated by comparing the CD intensities with those of the corresponding all-chiral amidine double helices with the same molecular lengths. Variable-temperature CD experiments of the all-chiral and chiral/achiral amidine duplexes demonstrated that the Pt(II)-linked complementary duplexes are dynamic and their chiroptical properties including the chirality transfer from the chiral amidine unit to the achiral amidine ones are significantly affected by the molecular lengths, sequences, and temperatures. On the basis of the above results together with molecular dynamics simulation results, key structural features of the Pt(II)-linked oligomer duplexes and the effect of the chiral/achiral amidine sequences on the amplification of chirality are discussed.

Terminal contributions for duplex oligonucleotide thermodynamic properties in the context of nearest neighbor models

Additive physical properties of DNA polymer duplexes have been expanded in terms of eight irreducible parameters that ultimately lead to consistency relations among the corresponding 10 duplex dimer contributions. End parameters are often added to allow for oligomer analysis which would add four extra degrees of freedom to the aforementioned parameters. Analysis of sufficient experimental data on oligomer duplexes allows for the unambiguous recovery of irreducible parameters. Values for free energy, enthalpy, and entropy are thus obtained, in terms of either irreducible or dimer decomposition sets. Here, a better adjust for the entropic (and enthalpic) irreducible parameters are obtained as we consider the more precise melting temperature data for the sequences of a given dataset. However, still large error estimates, and no clear distinction between the orientations of the terminal base pairs could yet be found. Finally, statistical mechanics approaches are applied for to connect the nearest neighbor approach to the two states model. Ad hoc end effects can be thus correlated to nucleation phenomena, leading to a critique for its role in nearest neighbor modeling.

ChemInform Abstract: Extended Aromatic Furan Amidino Derivatives as Anti-Pneumocystis carinii Agents.

The syntheses of nine new derivatives of 2,5-bis[4-(N-alkylamidino)phenyl]furans with extended aromatic systems are reported. The interaction of these dicationic furans with poly(dA)*poly(dT) and with the duplex oligomers d(CGCGAATTCGCG)2 and d(GCGAATTCGC)2 was determined by Tm measurement, and the effectiveness of these compounds against the immunosuppressed rat model of Pneumocystis carinii was evaluated. At a screening dose of 10 μmol/kg, 4 of the 12 amidino furans described here are more active than the parent compound 1. In general, extension of the aromatic system in the absence of a substitution of the amidino nitrogens resulted in higher affinity for DNA than the parent compound as judged by the larger ΔTm values and suggests enhanced van der Waals interactions in the amidino furan−DNA complex. Three of the compounds, 3, 5, and 11, yield cysts counts of less than 0.1% of control when administered at a dosage of 10 μmol/kg. Compound 3, which does not have an extended aromatic system, is the most ac...

Spontaneous self-assembly of nucleic acids: liquid crystal condensation of complementary sequences in mixtures of DNA and RNA oligomers

“Le cose tutte quante hanno ordine tra loro, e questo e’ forma che l’universo a Dio fa simigliante.” (Dante Alighieri, Divina Commedia, Paradiso, I, 103) [All things whate’er they be Have order among themselves, and this is form, That makes the universe resemble God] A remarkable example of spontaneous self-assembly of biomolecules, driven purely by physical interactions, is reported. Short, complementary DNA and RNA oligomers, down to six bases in length, exhibit lyotropic liquid crystal phases, chiral nematic and columnar, although these duplexes lack the shape anisotropy required for liquid crystal ordering. Such phases are produced by the end-to-end stacking of the duplex oligomers into polydisperse, anisotropic, rod-shaped aggregates, which can order into liquid crystals. Furthermore, when only a fraction of the sample is composed of complementary sequences, and hence the solution is effectively a mixture of single strands and double-stranded helices, the system is found to phase separate with duplex-rich liquid crystalline domains emerging from an isotropic background rich in single strands. This spontaneous partitioning, resulting from a combination of entropic and enthalpic factors, is sensitive to the degree of complementarity of the sequences and can be tuned with temperature. We suggest that in a chemical environment where oligomer ligation is possible, such ordering and condensation could provide a plausible route for the selective synthesis of extended complementary oligomers, a mechanism of possible relevance in prebiotic scenarios.