SEARCH · PubMed Health

Results for “G-quadruplex DNA”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

18 recordsLinked to original sources

PubMed2026

Peroxiredoxin 1 safeguards the nucleolar genome from oxidative damage.

Peroxiredoxin 1 (PRDX1) is a highly conserved, thiol-dependent peroxidase that rapidly scavenges reactive oxygen species to modulate redox signaling. PRDX1-null mice exhibited genomic instability, shortened life span, and accelerated tumorigenesis, including development of lymphomas, sarcomas, and carcinomas. Despite extensive characterization of these phenotypes, the molecular mechanism by which PRDX1 loss causes genomic instability remains poorly understood. Here, we show that PRDX1 deficiency alters nucleolar morphology, impairs RNA polymerase I (POL-I)-dependent transcription of pre-ribosomal RNAs, and triggers nucleolar genomic instability. This oxidative stress-induced nucleolar dysfunction promotes the stability of secondary DNA structures, such as RNA-DNA hybrids and G-quadruplex DNA, contributing to nucleolar genomic instability. We demonstrate that PRDX1 loss reduces nascent ribosomal RNA (rRNA) levels and impairs rRNA processing, further affecting ribosome biogenesis. Mechanistically, we established that PRDX1 loss triggers activation of the nucleolar DNA damage response characterized by activation of the DNA repair kinase ATM and elevated TCOF1 within the nucleolus. In addition, we observed recruitment of the MRE11-RAD50-NBS1 (MRN) complex subunit NBS1 to ribosomal DNA (rDNA) loci and this was further increased under oxidative stress. NBS1 accumulation correlates with the repression of rDNA transcription by POL-I, potentially delaying rRNA synthesis, and safeguarding the nucleolar genome from further oxidative damage. Collectively, these findings uncover a previously unrecognized, but critical role, for PRDX1 in maintaining nucleolar integrity and ribosomal biogenesis through redox-dependent regulation of rDNA transcription and processing machinery.

Oxidative Stress↗

PubMed2025

Post-transcriptional control of KRAS: functional roles of 5'UTR RNA G-quadruplexes, long noncoding RNA, and hnRNPA1.

Previous studies have shown that human KRAS expression is regulated at the transcriptional level by G-quadruplex DNA structures within its promoter. Here we show an additional level of regulation involving a post-transcriptional mechanism centred on the 5'-untranslated region (5'UTR) of the messenger RNA (mRNA) characterized by G4 structures (rG4s). Long noncoding RNAs (lncRNAs) and the protein hnRNPA1 are also involved in this mechanism. RIP-seq confirmed the presence of rG4s in the 5'UTR. Deletion of the rG4 region using CRISPR/Cas9 resulted in a significant increase in KRAS mRNA levels, indicating the role of the 5'UTR in controlling mRNA levels. RIP shows that hnRNPA1 is recruited to the 5'UTR, where it unfolds the rG4 structures and potentially affects mRNA stability. In addition, lncRNAs transcribed from the LINC01750 locus can hybridize to the rG4 region of 5'UTR and form RNA duplexes leading to RNase III-assisted degradation of the targeted mRNA. Activation of the LINC01750 locus with dCas9-VP64 resulted in downregulation of KRAS mRNA, whereas its suppression with dCas9-KRAB led to upregulation of both KRAS mRNA and protein. Since lncRNA-mediated regulation of mRNA appears to be a crucial aspect of cellular homeostasis and its disruption contributes to various diseases, understanding these mechanisms may reveal promising new therapeutic targets.

Humans↗

PubMed2026

Dual recognition drives site-directed G-quadruplex stabilization: Oligonucleotide design in G4 ligand-oligonucleotide conjugates.

G-quadruplex (G4) DNA structures are increasingly recognized for their roles in transcriptional regulation and genome stability, making them attractive therapeutic targets. Selective recognition of individual G4s remains challenging due to the high structural similarity among G4 motifs. G4 Ligand-Oligonucleotides conjugates (GL-Os) address this challenge by combining small-molecule G4 ligands with the sequence specificity of oligonucleotides, targeting sequences flanking the intended G4 target. Here, we systematically investigate how oligonucleotide length, backbone composition, and sequence complementarity govern GL-O binding, selectivity, and G4 stabilization. We show that effective G4 recognition depends on the interdependence between oligonucleotide hybridization and G4 ligand binding, such that both elements cooperatively reinforce complex stability and site specificity. Longer oligonucleotides promote more stable complexes and stronger G4 stabilization, whereas central mismatches disrupt this dual-recognition mechanism. Replacement of DNA with peptide nucleic acids (PNAs) enhances binding strength, thermal stability, and metabolic stability. Importantly, ligand conjugation redirects PNA oligonucleotides from nonspecific polymerase stalling toward selective G4 stabilization. Finally, we demonstrate receptor-mediated cellular uptake of modified GL-Os, supporting the feasibility of cellular delivery while highlighting remaining delivery barriers. Together, these findings show the molecular design principles governing GL-O behavior and provide a foundation for the future development and evaluation of selective G4-targeting therapeutics.

G-quadruplex DNA↗

PubMed2024

FANCJ DNA helicase is recruited to the replisome by AND-1 to ensure genome stability.

FANCJ, a DNA helicase linked to Fanconi anemia and frequently mutated in cancers, counteracts replication stress by dismantling unconventional DNA secondary structures (such as G-quadruplexes) that occur at the DNA replication fork in certain sequence contexts. However, how FANCJ is recruited to the replisome is unknown. Here, we report that FANCJ directly binds to AND-1 (the vertebrate ortholog of budding yeast Ctf4), a homo-trimeric protein adaptor that connects the CDC45/MCM2-7/GINS replicative DNA helicase with DNA polymerase α and several other factors at DNA replication forks. The interaction between FANCJ and AND-1 requires the integrity of an evolutionarily conserved Ctf4-interacting protein (CIP) box located between the FANCJ helicase motifs IV and V. Disruption of the CIP box significantly reduces FANCJ association with the replisome, causing enhanced DNA damage, decreased replication fork recovery and fork asymmetry in cells unchallenged or treated with Pyridostatin, a G-quadruplex-binder, or Mitomycin C, a DNA inter-strand cross-linking agent. Cancer-relevant FANCJ CIP box variants display reduced AND-1-binding and enhanced DNA damage, a finding that suggests their potential role in cancer predisposition.

Humans↗

PubMed2026

Conservation of Long G4-rich (LG4) genomic enhancer regulations.

Long G4-rich regions (LG4s) are defined as DNA sequences containing a high density of guanine triplets capable of forming non-B DNA structures called G-quadruplexes (G4s). These regions frequently overlap with enhancers, which are regulatory DNA elements that modulate gene expression by interacting with DNA regions that dictate where transcription is initiated known as promoters. While LG4s have now been well-characterized in the human genome, neither LG4 occurrence, nor the ability of LG4s to function as enhancers, in other species has been described. To address this, we screened the genomes of 16 different species from various taxa to identify LG4s and then determined if they were conserved, and additionally, we show the ability of one of the conserved LG4s to interact with its cognate promoter in vitro is functionally maintained across species. Our analyses characterized a number of previously unreported LG4s in the human genome as well as LG4s in 13 additional species. Of note, we identified a highly conserved LG4 enhancer predicted to regulate over 40 genes. This LG4 is embedded in the MAZ (Myc-Associated Zinc finger protein) locus, and we find this LG4 possesses the ability to directly interact with the same target promoter in both human and mouse. In summary, this work describes LG4s in the genomes of both unicellular and multicellular species including vertebrates, invertebrates, plants, and fungi, and finds many of these LG4 sequences highly conserved.

G-Quadruplexes↗

PubMed2026

Unraveling G-Quadruplex and i-Motif Coexistence Within a Double-Stranded DNA.

DNA can transiently fold into variable arrangements, which are expected to exploit regulatory functions. Guanine-rich sequences can fold into G-quadruplexes (G4s), while the complementary strand adopts potentially i-Motif (iM) arrangements. Their concomitant formation at the same genomic site is still under debate. However, recently, single-molecule analyses have shown the simultaneous G4 and iM presence within a double-stranded (ds) DNA context, addressing them as synergic blockers of replication fork progression. While these findings point to a functional interplay between G4 and iM, a deeper understanding of the factors enabling their coexistence remains unclear. In this work, we unravel the equilibria governing G4- and iM-folding within dsDNA, adopting an extensive biophysical approach allowing analysis of an optimized modular system, scalable across constructs of increasing molecular complexity. Our findings corroborate the simultaneous formation model and further clarify the thermodynamic determinants driving duplex denaturation and the favorable folding of stable G4 and iM structures.

G-Quadruplexes↗

PubMed2025

Hyperpolarized NMR Reveals Low-Populated Folding Intermediates in DNA.

Nuclear magnetic resonance (NMR) spectroscopy is the only biophysical technique capable of characterizing nucleic acid structures at atomic resolution under near-physiological liquid-state conditions. Still, it is fundamentally limited by intrinsically low sensitivity, particularly when analyzing high-molecular-weight, low-abundance, or polymorphic targets, such as DNAs (DNA). In this study, we demonstrate that hyperpolarized aqueous buffers generated via dissolution dynamic nuclear polarization (dDNP) significantly enhance the 1H NMR signals of multiple DNA motifs. The resonances of labile imino and amino protons of DNAs dissolved in hyperpolarized buffers are enhanced up to ∼200-fold and ∼370-fold, respectively. These intense signals serve a 2-fold purpose: (i) as structural fingerprints of DNA folding topologies and (ii) they enable the direct observation of low-populated folding intermediates in DNA polymorphs, such as G-quadruplexes (G4) and i-motifs (iM), which remain undetectable by standard methods. Thus, our findings establish hyperpolarized NMR as a high-sensitivity method for probing DNA structures and folding intermediates across a wide range of motifs, opening possible avenues in liquid biopsy applications and cell-free DNA.

DNA↗

PubMed2026

G-quadruplex upstream of PAX9 TSS acts as a 3D-genome scaffold to remotely silence X-linked genes and modulate cell-cycle progression.

G-quadruplexes (G4s) are non-canonical DNA secondary structures that act as local replication barriers and transcriptional regulators. Whether G4 can simultaneously influence splicing, DNA replication, and long-range, trans-chromosomal gene regulation remains untested. Here we combined in vitro biophysics, CRISPR mutagenesis and multi-omics to dissect a conserved G4 motif (QS1) located ~173 bp upstream of the PAX9 transcription start site. CD spectroscopy confirmed that the wild-type, but not the G-to-T mutant sequence, folds into a stable parallel G4 under physiological K+. In human cells, disruption of the QS1 G4 changed chromatin accessibility, remotely down-regulated a cohort of X-linked genes, accelerated migration and delayed G1/S progression. Integrative analysis of ATAC-seq, RNA-seq profiling reveals that the QS1 G4 acts as a three-dimensional genome scaffold linking PAX9 to cell-cycle and metabolic networks. Our findings establish a pleiotropic role for a single promoter G4 in coordinating DNA replication stress, chromatin architecture and trans-chromosomal transcriptional control.

G-Quadruplexes↗

PubMed2026

G-quadruplex structures as regulators of cellular processes and drivers of genome instability in cancer.

G-quadruplexes (G4s) are essential regulatory structures whose biological functions are inseparable from their potential to destabilize the genome. They play critical roles in transcription, replication and chromatin architecture, yet they also contribute to the genomic instability that fuels cancer. This dual role is an inherent consequence of where G4s form in the genome. G4s are enriched at highly active regulatory regions, including promoters, replication origins and topologically associated domain boundaries, where their controlled formation and resolution by helicases and topoisomerases support normal genome function. When this control is lost, the same features that make G4s functional become harmful, leading to R-loop and G-loop accumulation, replication fork stalling and increased conflicts between transcription and replication. Topoisomerase activity, which normally relieves supercoiling stress, can instead generate the DNA double-strand breaks that characterize cancer genomes. Persistent G4 structures also promote micronuclei formation and cytoplasmic DNA accumulation, activating the cGAS-STING innate immune signaling pathway. Here, we discuss these mechanisms and present pan-cancer genomic analyses showing that these processes operate broadly across human tumors. Therapeutically targeting G4s requires balancing their essential regulatory roles with their pathological effects. Understanding this tension is therefore essential for exploiting G4s as therapeutic targets across cancer types.

DEAH-box helicases↗

PubMed2024

Viral hijacking of hnRNPH1 unveils a G-quadruplex-driven mechanism of stress control.

Viral genomes are enriched with G-quadruplexes (G4s), non-canonical structures formed in DNA or RNA upon assembly of four guanine stretches into stacked quartets. Because of their critical roles, G4s are potential antiviral targets, yet their function remains largely unknown. Here, we characterize the formation and functions of a conserved G4 within the polymerase coding region of orthoflaviviruses of the Flaviviridae family. Using yellow fever virus, we determine that this G4 promotes viral replication and suppresses host stress responses via interactions with hnRNPH1, a host nuclear protein involved in RNA processing. G4 binding to hnRNPH1 causes its cytoplasmic retention with subsequent impacts on G4-containing tRNA fragments (tiRNAs) involved in stress-mediated reductions in translation. As a result, these host stress responses and associated antiviral effects are impaired. These data reveal that the interplay between hnRNPH1 and both host and viral G4 targets controls the integrated stress response and viral replication.

Animals↗

PubMed2026

Oxidative Damage Fine-Tunes G-Quadruplex Structures in Human Gene Promoters.

Oxidative damage can convert guanine (G) into 8-oxoguanine (O8G), resulting in altered gene expression and genome instability. However, the underlying molecular mechanisms remain poorly understood. Herein, we show that the NEIL3 gene proximal promoter sequence forms a mixture of parallel and hybrid G-quadruplex structures (NEIL3-G4s), exhibiting intrinsic structural polymorphism. Strikingly, site-specific O8G modifications significantly reduce this polymorphism, promoting the stabilization of either the parallel or the (3+1) hybrid-1 G4 topology. A single G-to-O8G substitution is sufficient to trigger a clear structural transition from the parallel to the (3+1) hybrid-1 G4, highlighting the profound impact of O8G on G4-mediated epigenetic regulation. We have determined the NMR solution structures of both native and O8G-modified NEIL3-G4s, providing mechanistic insights into how O8G induces specific G4 structural rearrangements. Functional analysis demonstrates that both forms of NEIL3-G4s can form in extended DNA contexts and inhibit DNA polymerase activity. Under oxidative stress, the formation of NEIL3-G4s correlates with elevated NEIL3 gene expression, suggesting that they play a role as sensors of oxidative damage and function as molecular switches for gene upregulation. Collectively, these findings underscore the crucial role of O8G-induced G4 structural plasticity in the cellular response to oxidative stress and in regulating gene expression.

G-Quadruplexes↗

PubMed2026

DNM1L depletion leads to accelerated heteroplasmy shifting of m.10191C allele through ATG7-dependent pathways.

Nucleotide composition bias in mitochondrial DNA (mtDNA) makes the heavy strand prone to form a DNA secondary structure called a guanine quadruplex (G4). This secondary structure has been shown to inhibit polymerase processivity in vitro. We previously identified pathogenic mtDNA variants that lead to increased G4-forming propensity, including a T to C mutation at m.10191 (m.10191 T > C) that causes Leigh syndrome. Cells treated with G4 binding agent (G4BA) berberine show a reduction in m.10191C pathogenic heteroplasmy levels. To help better understand the underlying mechanism behind berberine-induced heteroplasmy shift, we examined the relationship between mitochondrial fission and berberine-mediated shift. Here we show that knockdown of the fission factor DNM1L leads to an accelerated heteroplasmy shift towards the healthy mtDNA allele, lowering m.10191C by 10% in 3 weeks, compared to the 5 weeks required for berberine alone. The specific mechanism involves ATG7, as knockdown of ATG7 is able to partially delay this accelerated heteroplasmy shift. Taken together, we show that DNM1L knockdown is able to accelerate berberine-induced m.10191C heteroplasmy shifting through an autophagy-related mechanism.

Humans↗

PubMed2025

Prediction and functional interpretation of inter-chromosomal genome architecture from DNA sequence with TwinC.

Three-dimensional nuclear DNA architecture comprises well-studied intra-chromosomal (cis) folding and less characterized inter-chromosomal (trans) interfaces. Current predictive models of 3D genome folding can effectively infer pairwise cis-chromatin interactions from the primary DNA sequence but generally ignore trans contacts. There is an unmet need for robust models of trans-genome organization that provide insights into their underlying principles and functional relevance. We present TwinC, an interpretable convolutional neural network model that reliably predicts trans contacts measurable through proximity ligation-dependent (in situ and intact Hi-C) and independent (DNA SPRITE) genome-wide chromatin conformation assays. . TwinC uses a paired sequence design from replicate Hi-C experiments to learn single base pair relevance in trans interactions across two stretches of DNA. The method achieves high predictive accuracy (AUROC=0.80) on a cross-chromosomal test set from in situ and intact Hi-C experiments in heart tissue. Furthermore, we train TwinC using in situ Hi-C data from the widely used GM12878 cell line and validate its performance with orthogonal DNA SPRITE assay in the same cell type. Mechanistically, the neural network learns the importance of compartments, chromatin accessibility, clustered transcription factor binding and G-quadruplexes in forming trans contacts. In summary, TwinC models and interprets trans genome architecture, shedding light on this poorly understood aspect of gene regulation.

Journal Article↗

PubMed2025

G4STAB: a multi-input deep learning model to predict G-quadruplex thermodynamic stability based on sequence and salt concentration.

MOTIVATION: G-quadruplexes (G4s) are non-canonical nucleic acid structures formed in guanine-rich regions that modulate gene regulation and genomic stability. The thermodynamic stability of G4s directly influences their biological functions and potential as therapeutic targets. However, current quantitative frameworks for predicting G4 stability rely on predetermined structural features, limiting their effectiveness for diverse G4 topologies, and fail to account for environmental factors such as ion concentration and pH that significantly modulate G4 stability in cellular contexts. RESULTS: We present G4STAB, a multi-input deep learning neural network that accurately predicts DNA G4 melting temperatures based on sequence features, salt concentration, and pH. Trained on 2382 diverse DNA G4 sequences, our model achieves high accuracy (R 2=0.8) without relying on predetermined G4 structural features. G4STAB successfully captures established G4 stability determinants and proposes previously unobserved sequence-stability relationships. Analysis of 391 502 experimentally validated G4s reveals that cancer-like ionic environments alter G4 stability profiles, with a 13.5-fold increase in the number of structures exhibiting physiological melting temperatures (36-42°C). These findings suggest systematic genomic patterns in G4 stability responses across chromosomes and gene types. AVAILABILITY AND IMPLEMENTATION: G4STAB is available at https://github.com/donn-liew/G4STAB; G4STAB web database interface is available at https://donn-liew.github.io/g4stab-web-database/.

G-Quadruplexes↗

PubMed2024

Role of RNA G-Quadruplexes in the Japanese Encephalitis Virus Genome and Their Recognition as Prospective Antiviral Targets.

G-quadruplexes (GQs) have been primarily studied in the context of cancer and neurodegenerative pathologies. However, recent research has shifted focus to their existence and functional roles in viral genomes, revealing GQ-regulated key pathways in various human pathogenic viruses. While GQ structures have been reported in the genomes of emerging and re-emerging viruses, RNA viruses have been understudied compared to DNA viruses, including notable examples such as human immunodeficiency virus-1, hepatitis C virus, Ebola virus, Nipah virus, Zika virus, and SARS-CoV-2. The flavivirus family, comprising the Japanese encephalitis virus (JEV), poses a significant global threat due to recurring outbreaks yet lacks approved antivirals. In this study, we identified and characterized eight putative G-quadruplex-forming motifs within essential genes involved in genome replication, assembly, and internalization in the host cell, conserved across different JEV isolates. The formation and stability of these motifs were validated through a multitude of biophysical and cell-based assays. The interaction and binding affinity of these motifs with the known GQ-binding ligand BRACO-19 were supported by biophysical assays, confirming the capability of these motifs to form GQ structures. Notably, BRACO-19 also exerted antiviral properties through reduction of viral replication and infectious virus titers as well as inhibition of viral protein expression, as evaluated by the cell-based assays. This comprehensive molecular characterization of G-quadruplex structures within the JEV genome highlights their potential as promising antiviral targets for intervention strategies against JEV infection through GQ-specific ligands.

G-Quadruplexes↗

PubMed2026

Identification of a G-quadruplex-forming cell-free DNA fragment as a biomarker for the precise diagnosis of hepatocellular carcinoma.

Early detection of hepatocellular carcinoma (HCC) remains challenging, as the currently recommended surveillance strategy based on ultrasound combined with alpha-fetoprotein (AFP) is limited by suboptimal sensitivity and accessibility. Cell-free DNA (cfDNA) provides a minimally invasive avenue for cancer detection. However, most existing cfDNA-based approaches either perform unreliably in low-input samples or require analytically complex workflows. Here, we systematically profiled serum cfDNA from individuals with HCC and without HCC and identified a high-abundance tumor-associated single cfDNA fragment at the FAM230F genomic region. Integrative analysis of liver assay for transposase-accessible chromatin with sequencing (ATAC-seq) data revealed consistent tumor-specific chromatin accessibility at this locus, suggesting a tumor-derived origin. Structural characterization further demonstrated enrichment of G-quadruplex (G4) features within the target sequence, which may increase resistance to serum nuclease degradation and promote its preferential retention in circulation. Based on these properties, we established a qPCR-based detection workflow with clinical accessibility. In a validation cohort independent of the discovery cohort, a ΔC t cutoff of 2 was selected by maximizing the Youden index within the same cohort. The assay showed a sensitivity of 94.5% and a specificity of 90.5% for distinguishing HCC from non-HCC. Collectively, our study identifies FAM230F as a structurally stable tumor-associated cfDNA fragment and establishes a simple and scalable qPCR-based assay for HCC detection, providing a practical framework for translating cfDNA fragment analysis into clinical biomarkers.

Journal Article↗

PubMed2026

B-MYB (MYBL2): from cell cycle regulator to an oncogenic player.

B-MYB (MYBL2) is a transcription factor of the MYB family that plays critical roles in cell cycle progression, proliferation, and survival. Through the DREAM-MMB-FOXM1 network, B-MYB coordinates the expression of genes required for mitosis and cytokinesis (G2/M genes), while genes required for DNA replication during S phase are regulated by E2F-DP complexes. Initially identified as a regulator of normal cell cycle processes, B-MYB has emerged as a key oncogenic driver across multiple cancer types. This review addresses the physiological roles of B-MYB, the mechanisms underlying its oncogenic activation, and its contributions to tumorigenesis and clinical relevance as a prognostic biomarker and potential therapeutic target. Aberrant activation of B-MYB, driven by gene amplification, transcriptional upregulation, or post-translational modification, is reported as a recurrent feature of aggressive cancers. The consequences of B-MYB overexpression, including uncontrolled proliferation, genomic instability, apoptosis evasion, epithelial-to-mesenchymal transition, therapy resistance and metabolic reprogramming, further underscore B-MYB as a central oncogenic driver. Clinically, B-MYB overexpression correlates with poor prognosis, advanced disease and chemoresistance across multiple malignancies. Thus, we aim to emphasise the biological roles of B-MYB in physiological and cancer mechanisms, alongside the growing evidence establishing it as both a biomarker of disease and a potential therapeutic target. While previous reviews have addressed isolated aspects of B-MYB biology, this review provides a comprehensive and updated integration of recent mechanistic advances (A-MYB/B-MYB functional redundancy and YAP/TAZ-TEAD crosstalk) and the therapeutic potential of non-canonical DNA structures at the B-MYB promoter. We further review current trends and methodologies for targeting B-MYB and outline new perspectives for future therapeutic research.

Humans↗

PubMed2026

Symmetric and near-symmetric cyanine probes for G-quadruplexes: molecular recognition, signal transduction, and biological applications.

G-quadruplexes (G4s) are dynamic noncanonical nucleic-acid structures involved in genome maintenance, transcription, RNA metabolism, and mitochondrial function, and are implicated in disease-associated processes. Symmetric and near-symmetric cyanines are versatile platforms for G4 recognition because their polymethine length, terminal heterocycles, charge distribution, conformational freedom, and supramolecular organization can be systematically tuned within related scaffolds. This review discusses how these structural features control G4 recognition and optical signal transduction through terminal G-tetrad stacking, loop and groove contacts, restriction of molecular motion, and aggregate reorganization. We first summarize in vitro recognition, structural discrimination, and G4-mediated sensing, and then discuss DNA and RNA G4 imaging, G4-associated biological processes, and emerging in vivo applications. Particular attention is given to several distinctions that are essential for interpreting probe performance: binding affinity versus fluorescence activation, topology preference versus DNA/RNA selectivity, organelle accumulation versus molecular targeting, and imaging contrast versus biological validation. Overall, molecular symmetry is considered a tunable design variable rather than a direct predictor of performance. Future studies should emphasize matched structural series, reversible and minimally perturbing probes, optical readouts that are less dependent on probe concentration, clear separation of DNA and RNA contributions, and standardized validation across solution, cellular, and whole-organism studies.

Journal Article↗