Biology subjects

Rodriguez, A.

Publications and source records attributed to Rodriguez, A..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

A patient derived xenograft repository capturing clinical and molecular heterogeneity of large B-cell lymphoma

Large B-cell lymphomas (LBCLs) are a clinically and molecularly diverse group of malignancies with a rapidly evolving therapeutic landscape that has introduced new areas of clinical need such as post-CD19 chimeric antigen receptor T (CART19) progression. Patient derived xenograft (PDX) models are an important tool for mechanistic studies and preclinical evaluation of new therapies and can be generated from a variety of clinical contexts that capture tumor-intrinsic resistance mechanisms. We therefore undertook a comprehensive effort to generate PDX models that encompass the molecular landscape of LBCLs and include important clinical scenarios for new drug development. Here we describe the first 48 models within this publicly available repository, capturing the transcriptional and genetic subsets of LBCL. These models also include 23 generated from post-CART progression biopsies which reproduce patterns of progression driven by CD19 mutation or expression loss, as well as tumor cell-intrinsic CART19 resistance that we validate in vivo. STATEMENT OF SIGNIFICANCEYang et al. describe X-LYMPH (Xenografts of Lymphoma), a publicly available and molecularly annotated PDX repository that captures the heterogeneity of large B-cell lymphoma. X-LYMPH includes models of chimeric antigen receptor T cell resistance, providing a shared foundation for mechanistic research and therapeutic development for lymphomas.

cancer biology↗

bioRxiv2025

Bad bugs, new drugs: The antimicrobial peptide C14R is active against the ESKAPE pathogens

The global rise of antimicrobial resistance among the ESKAPE pathogens represents a major challenge to public health. Here, we report the broad-spectrum antibacterial activity of the synthetic antimicrobial and pore-forming peptide C14R against all six ESKAPE species. Using a radial diffusion assay and resazurin-based viability testing, C14R exhibited potent bactericidal effect with minimum inhibitory concentrations (MICs), defined as the lowest concentration of an antimicrobial agent that completely inhibits visible growth of planktonic microorganisms, ranging from 3.4 g/mL (Enterococcus faecium, vancomycin-resistant) to 45.2 g/mL (Klebsiella quasipneumoniae, ESBL). C14R also inhibited biofilm formation by Gram-positive pathogens, with minimum biofilm inhibitory concentrations (MBICs), referring to the minimal concentration required to prevent the development of biofilms, of 15.0 g/mL (Staphylococcus aureus, MRSA) and 22.0 g/mL (E. faecium, VRE), whereas Gram-negatives biofilms showed higher tolerance. Together, these findings demonstrate that C14R retains high activity against multidrug-resistant ESKAPE strains, highlighting its potential as a lead compound for the development of next-generation antimicrobial drugs to expand the portfolio of available antibiotics and brace health systems against emerging severe infections. Author summaryAntibiotic-resistant infections are a growing threat worldwide. A small group of hospital-associated bacteria is especially problematic because they often evade multiple drugs and cause hard-to-treat infections. In this study, we tested the designed antimicrobial peptide C14R as a novel and effective way to fight these bacteria. Peptides are short protein fragments with the ability to puncture and disrupt microbial membranes. We evaluated C14R against six hospital related priority species (so called ESKAPE pathogens) and measured its ability to stop growth and to limit biofilm formation. C14R killed every species we tested and reduced biofilm of two bacteria. Our findings identify C14R as a promising lead for new treatments, particularly for difficult infections and those involving biofilms.

microbiology↗

bioRxiv2025

An InDel Genomic Variant within a Bifunctional Super-Enhancer for LINC00636 and CD47 Regulation in Breast Cancer

Highly accessible genomic super-enhancers often drive tumor-promoting programs, yet the impact of genomic variation within these regulatory elements remains unclear. Here, we identified a bifunctional super-enhancer that regulates the expression of cancer-promoting genes LINC00636 and CD47 in breast cancer. We discovered that a common germline insertion variant within the super-enhancer is associated with reduced chromatin accessibility at the super-enhancer locus. Deletion of the insertion in breast cancer cells increased chromatin accessibility, leading to upregulation of LINC00636 and CD47, enhanced resistance to nutrient-deprivation-induced apoptosis (mediated by CD47), activation of senescence (driven by elevated LINC00636), delayed cell death, and reduced infiltration of CD80 pro-inflammatory macrophages, changes that represent tumor-promoting features. Together, our findings uncover a common insertion-deletion variant that fine-tunes the regulatory activity of a bifunctional super-enhancer, suggest a protective role for the insertion allele, and establish a novel function for LINC00636 in senescence and breast cancer.

genomics↗

bioRxiv2025

Diurnal plant and Rhizophagus irregularis transcriptional patterns are linked to shifts in cassava tissue partitioning in the field

O_LICassava is a globally-important crop whose yields can radically increase with arbuscular mycorrhizal fungi (AMF) inoculation. However, extensive background noise in field environments makes it very challenging to understand how the cassava-AMF symbiosis confers benefits, which is especially important for future applications of AMF treatments. C_LIO_LIIn two field experiments, we combined transcriptomics and allometric analyses to investigate functional variation in cassava-AMF interactions using sterile, single isolates of Rhizophagus irregularis. We developed a novel Index of Symbiotic Transcriptional Activity (ISTA) and accounted for sampling times to reduce transcriptomic noise and improve links to biomass traits. C_LIO_LIISTA significantly correlated with cassava shoot biomass in an isolate-dependent manner, and allometric analyses revealed that R. irregularis isolates can either reinforce or uncouple cassava shoot-root relationships to maximize root yields. Differential expression and co-expression network analyses uncovered isolate-specific plant and fungal gene module responses. Including ISTA and sampling time as random effects enhanced detection of gene candidates, including down-regulated genes linked to higher yield. C_LIO_LIOur study uses novel and translatable transcriptomic tools to readily dissect variably field data, allowing new links to be found between AMF symbiotic functions and cassava yields. C_LI

molecular biology↗

bioRxiv2025

Retinol Binding Protein 4 reactivates latent HIV-1 via the JAK/STAT5 and JNK pathways

Reactivation of the latent viral reservoirs is crucial for a cure of HIV/AIDS. However, current latency reversing agents are inefficient and the endogenous factors that have the potential to reactivate HIV in vivo remain poorly understood. To identify natural activators of latent HIV-1, we screened a comprehensive peptide/protein library derived from human hemofiltrate, representing the entire blood peptidome, using J-Lat cell lines harboring transcriptionally silent HIV-1 GFP reporter viruses. Fractions potently reactivating HIV-1 from latency contained human Retinol Binding Protein 4 (RBP4), the carrier of retinol (vitamin A). We found that retinol-bound holo-RBP4 but not retinol-free apo-RBP4 strongly reactivates HIV-1 in a variety of latently infected T cell lines. Functional analysis revealed that this reactivation depends on the JAK/STAT5 and JNK pathways but does not require retinoic acid production. High levels of RBP4 were detected in plasma from both healthy individuals and people living with HIV-1. Physiological concentrations of RBP4 induced significant viral reactivation in latently infected cells from individuals on long-term antiretroviral therapy with undetectable viral loads. As a potent natural HIV-1 latency-reversing agent, RBP4 offers a novel approach to activating the latent reservoirs and bringing us closer to a cure.

immunology↗

bioRxiv2025

The emerging fungal pathogen Candida auris induces IFNγ to colonize mammalian hair follicles

Public health alarm concerning the emerging fungus Candida auris is fueled by its antifungal drug resistance and propensity to cause deadly outbreaks. Persistent skin colonization drives transmission and lethal sepsis although its basis remains mysterious. We compared the skin colonization dynamics of C. auris with its relative C. albicans, quantifying skin fungal persistence and distribution and immune composition and positioning. C. auris displayed a higher propensity to colonize hair follicles and avidly bound to human hair. While C. albicans triggered an effective sterilizing type 3/17 antifungal immune response driven by IL-17A/F-producing lymphocytes, C. auris triggered a type 1, IFN{gamma}-driven immune response targeting hair follicles. Rather than promoting fungal clearance, IFN{gamma} enhanced C. auris skin colonization by acting directly on keratinocytes impairing epithelial barrier integrity and repressing antifungal defense programs. C. auris exploits focal skin immune responses to create a niche for persistence in hair follicles.

immunology↗

bioRxiv2025

Nuclear Speckle Dynamics are Controlled by Polyphosphate Inhibition of CLK Proteins

Nuclear speckles (NS) are membrane-less nuclear organelles that act as critical hubs for pre-mRNA splicing. Defects in splicing are linked to several human diseases, including cancer, Alzheimers disease, and dystrophies. While CLK kinases regulate the mobilization of splicing factors from NS, the molecular mechanisms underlying NS assembly and dissolution remain unclear. Using an adaptation of the Biotinylation by Antibody Recognition (BAR) technique, we identify polyphosphate (polyP) as a novel and essential regulator of NS dynamics. Polyphosphate, a highly conserved polyanion composed of a chain of phosphate molecules, is involved in several functions in mammalian cells. Here, we show that polyP interacts with the NS core component SRRM2, and polyP depletion disrupts NS organization releasing splicing factors into the nucleoplasm. RNA-seq analysis reveals that polyP depletion increases exon inclusion, particularly in long genes with multiple exons, highlighting its role in splicing regulation. Mechanistically, we demonstrate that polyP acts as a physiological inhibitor of CLK3 kinase, preventing the phosphorylation of SR proteins and thereby maintaining NS stability. Our findings not only expand our understanding of NS biology but also provide new insights into the polyP involvement in splicing-related diseases. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=90 SRC="FIGDIR/small/633116v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@1dc44b6org.highwire.dtl.DTLVardef@2339e4org.highwire.dtl.DTLVardef@ade454org.highwire.dtl.DTLVardef@69482b_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2024

Early exposure to Western diet exacerbates visual outcomes in female mice.

Obesity, a growing pandemic in Western societies, significantly impacts metabolic health and contributes to visual disorders. While the systemic consequences of obesity, such as chronic inflammation and insulin resistance, are well-studied in adults, its early-life effects on retinal health remain underexplored. Using a maternal Western Diet (WD) exposure model, we investigated the developmental impact of early-life metabolic disturbances on retinal and cognitive function. Our findings reveal that WD exposure from gestation to early adulthood accelerates the onset of features resembling diabetic retinopathy, including increased retinal vascularization, inflammation, and compromised blood-retina barrier integrity, observed within just four months. Females exhibited heightened vulnerability, showing pronounced ocular defects such as anophthalmia, microphthalmia, and congenital cataracts. These results underscore a critical developmental window during which metabolic disruptions predispose to sex-specific retinal and neurovascular pathologies. This work bridges the link between pediatric and adult obesity, highlighting the urgent need for early interventions to mitigate long-term visual impairments that could further impair recognition memory.

physiology↗

bioRxiv2024

Optogenetic stimulation of a cortical biohybrid implant guides goal directed behavior

Brain-computer interfaces (BCIs) hold exciting therapeutic potential, but tissue damage caused by probe insertion limits channel count. Biohybrid devices, in which the cell-device interface is crafted in the laboratory, hold promise to address this limitation, but these devices have lacked a demonstration of their applicability for BCI. We developed a biohybrid approach to engraft optogenetically-enabled neurons on the cortical surface housed in a 2D-scaffold of circular microwells. The engrafted neurons survived, exhibited spontaneous activity, and integrated with the host brain several weeks after implantation. We then trained mice with biohybrid implants to perform an optical stimulation task and showed that they could effectively report optogenetic stimulation of their neural graft. This demonstration shows that a cortical biohybrid implant can be used to transmit information to the brain of an implanted animal.

neuroscience↗

bioRxiv2024

Influence of metal ions on the isothermal self-assembly of DNA nanostructures

DNA nanostructures are typically assembled by thermal annealing in buffers containing magnesium. We demonstrate the assembly of DNA nanostructures at constant temperatures ranging from 4 {degrees}C to 50 {degrees}C in solutions containing different metal ions. The choice of metal ions and the assembly temperature influence the isothermal assembly of several DNA motifs and designed three-dimensional DNA crystals. Molecular dynamics simulations show more fluctuations of the DNA structure in select monovalent ions (Na+ and K+) compared to divalent ions (Mg2+ and Ca2+). A key highlight is the successful assembly of DNA motifs in nickel-containing buffer at temperatures below 40 {degrees}C, otherwise unachievable at higher temperatures, or using an annealing protocol. DNA nanostructures isothermally assembled in different ions do not affect the viability of fibroblasts, myoblasts, and myotubes and or the immune response in myoblasts. The use of ions other than the typically-used magnesium holds key potential in biological and materials science applications that require minimal amounts of magnesium.

bioengineering↗

bioRxiv2024

Cell-scale porosity in microporous annealed particle (MAP) scaffolds modulates immune response and promotes formation of innervated muscle fibers in volumetric muscle loss injuries

Volumetric muscle loss (VML) is caused by severe traumatic injuries to skeletal muscle and is characterized by the irreversible loss of contractile tissue and permanent functional deficits. VML injuries cannot be healed by endogenous mechanisms and are exceptionally difficult to treat in the clinic due to the excessive upregulation of the inflammatory response, which leads to fibrosis, denervation of muscle fibers, and impaired regeneration. These injuries lead to long-term disability. Using a rodent model of VML in the tibialis anterior, this study presents microporous annealed particle (MAP) hydrogel scaffolds as a biomaterial platform for improved muscle regeneration in VML injuries, specifically highlighting the benefits of cell-scale porosity. In contrast to bulk (i.e., nanoporous) hydrogel scaffolds, MAP scaffolds promote integration by avoiding the foreign body response, decreasing the rate of implant degradation, and shifting macrophage polarization to favor regeneration. In addition, cell migration and angiogenesis throughout the implant precede the degradation of MAP scaffolds, including the formation of muscle fibers and neuromuscular junctions within MAP scaffolds prior to degradation. These fibers and junctions continue to develop as the implant degrades, indicating that MAP hydrogel scaffolds are a promising therapeutic approach for VML injuries.

bioengineering↗

bioRxiv2024

Deficiency of the hemoglobin-haptoglobin receptor, CD163, worsens insulin sensitivity in obese male mice

Excessive iron accumulation in metabolic organs such as the adipose tissue, liver, and skeletal muscle is associated with increased diabetes risk. Tissue-resident macrophages serve multiple roles including managing inflammatory tone and regulating parachymal iron homeostasis; thus protecting against metabolic dysfunction upon iron overload. The scavenger receptor CD163 is uniquely present on tissue-resident macrophages, and plays a significant role in iron homeostasis by clearing extracellular hemoglobin-haptoglobin complexes, thereby limiting oxidative damage caused by free hemoglobin in metabolic tissues. We show that the absence of CD163 exacerbates glucose intolerance and insulin resistance in male mice with obesity. Additionally, loss of CD163 reduced the expression of iron regulatory genes (Tfr1, Cisd1, Slc40a1) in adipose tissue macrophages and anti-inflammatory (M2-like) bone marrow-derived macrophages (BMDMs). Further, CD163 deficiency mediated a pro-inflammatory shift and limited hemoglobin scavenging specifically in M2-like BMDMs. To this end, iron buffering was diminished in inguinal white adipose tissue (iWAT) macrophages in vivo, which culminated in iron spillover into adipocytes and CD45+CD11B- non-myeloid immune cells in iWAT. These findings show that CD163 on tissue-resident macrophages is critical for their anti-inflammatory and hemoglobin scavenging roles, and its absence results in impaired systemic insulin action in an obese setting. Article HighlightsO_LILoss of CD163 mediates a phenotypic switch in M2-like macrophages towards a pro-inflammatory state. C_LIO_LICD163 is involved in free hemoglobin uptake and catabolism as well as oxidative metabolism, specifically in M2-like macrophages. C_LIO_LIIn inguinal white adipose tissue (iWAT) of CD163 defficient mice, macrophage iron is reduced; while concomitantly, adipocyte and other immune cell iron content is increased. C_LIO_LILoss of CD163 provokes glucose intolerance and insulin resistance in obese male mice. C_LI

physiology↗

bioRxiv2024

Let-7 restrains an oncogenic epigenetic circuit in alveolar type 2 cells to prevent ectopic formation of fibrogenic AT2 intermediates and pulmonary fibrosis

Analysis of lung alveolar type 2 (AT2) progenitor stem cells has highlighted fundamental mechanisms that direct their differentiation into alveolar type 1 cells (AT1s) in lung repair and disease. However, microRNA (miRNA) mediated post-transcriptional mechanisms which govern this nexus remain understudied. We show here that the let-7 miRNA family serves a homeostatic role in governance of AT2 quiescence, specifically by preventing the uncontrolled accumulation of AT2 transitional cells and by promoting AT1 differentiation. Using mice and organoid models, we demonstrate genetic ablation of let-7a1/let-7f1/let-7d cluster (let-7afd) in AT2 cells prevents AT1 differentiation and results in accumulation of AT2 transitional cells in progressive pulmonary fibrosis. Integration of AGO2-eCLIP with RNA-sequencing from AT2 cells uncovered the induction of direct targets of let-7 in an oncogene feed-forward regulatory network including BACH1/EZH2/MYC which drives an aberrant fibrotic cascade. Additional analyses using CUT&RUN-sequencing revealed an epigenetic role of let-7 in induction of chromatin histone acetylation and methylation and maladaptive AT2 cell reprogramming. This study identifies let-7 as a key gatekeeper of post-transcriptional and epigenetic chromatin signals to prevent AT2-driven pulmonary fibrosis.

cell biology↗

bioRxiv2024

The new SH3_T domain increases the structural and functional variability among SH3b-like CBDs from staphylococcal phage endolysins

Endolysins, proteins encoded by phages to lyse their hosts and release their progeny, have evolved to adapt to the structural features of each host. The endolysins from Staphylococcus-infecting phages typically feature complex architectures with two enzymatically active domains (EADs) and one cell wall-binding domain (CBD) belonging to the bacterial SH3 (SH3b) superfamily. This study focuses on three SH3b-like CBDs from exemplary staphylococcal phage endolysins (LysRODI, LysC1C, and LysIPLA5) that were structurally and functionally characterized. While RODI_CBD and C1C_CBD were assigned to the well-known SH3_5 family, a new family, SH3b_T, was identified using the CBD from LysIPLA5 as a model. GFP-fused CBDs were created to assess their differential binding to a collection of staphylococcal strains. IPLA5_CBD showed enhanced binding to Staphylococcus epidermidis, while RODI_CBD and C1C_CBD exhibited distinct binding profiles, with RODI_CBD targeting Staphylococcus aureus specifically and C1C_CBD displaying broad binding. Sequence comparisons suggested that a few differences in key amino acids could be responsible for the latter binding difference. The CBDs modulated the activity spectrum of synthetic EAD-CBD combinations in accordance with the previous binding profiles, but in a manner that was also dependent on the EAD present in the fusion protein. These results serve as a context for the diversity and versatility of SH3b domains in staphylococcal endolysins, providing insights on how (i) the CBDs from this superfamily have diverged to adapt to diverse bacterial ligands in spite of sharing a common fold; and (ii) the evolution of specificity relies on the EAD-CBD combination rather than solely the CBD. IMPORTANCEClinical management of bacterial infections is nowadays compromised by the rise in antimicrobial resistance. The development of new antimicrobial therapies with diverse modes of action is therefore of pivotal importance to complement the current standard of care. Phage endolysins are a new class of antibacterial agents based on rapid peptidoglycan degradation. The natural reservoir of phage endolysins offers a practically infinite diversity. This works reveals a broadly spread but still unknown phage endolysin domain targeting staphylococci while providing structural-functional insights that are paramount to understand the evolution of endolysins and how they can be applied as an antimicrobial.

molecular biology↗

bioRxiv2024

Do seabirds dream of artificial lights? Understanding light preferences of Procellariiformes

Seabirds, and particularly fledglings of burrow-nesting species, are greatly impacted by light pollution. During their inaugural flights from colony to sea, fledglings become grounded after encountering artificial light. Such groundings, or fallout events, affect many fledglings each year. To mitigate this light induced mortality, rescue programs have been implemented for decades in many locations worldwide. Despite the notoriety of fallouts, the contributing behavioural and biological factors remain mostly unknown. How do the mechanisms of light attraction and light avoidance interact or how do they manifest in different groups (e.g., age, personality, populations), or light pollution levels, remain open questions. We tested behavioural preferences of Corys shearwater Calonectris borealis fledglings, rescued after being grounded in urban areas, and of breeding adults, for contrasting light sources. Fledglings and adults were exposed to one of the three treatments in an experimental y-maze set-up: white light versus no-light, blue versus red light, and a control with no-light on each arm of the y-maze. Both age groups have shown preferences for the no-light arms and the red light arm. The preference for longer wavelengths and darker environments, along with slower responses by fledglings, suggest that close range light pollution appears to cause disorientation in seabirds. Our study helps to clarify the behavioural components of fallouts and provides further evidence on the disruptive effects of nocturnal artificial light on sensitive species.

animal behavior and cognition↗

bioRxiv2024

The relationship between gut and nasopharyngeal microbiome composition can predict the severity of COVID-19

Coronavirus disease 2019 (COVID-19) is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that displays great variability in clinical phenotype. Many factors have been described to be correlated with its severity, and microbiota could play a key role in the infection, progression, and outcome of the disease. SARS-CoV-2 infection has been associated with nasopharyngeal and gut dysbiosis and higher abundance of opportunistic pathogens. To identify new prognostic markers for the disease, a multicenter prospective observational cohort study was carried out in COVID-19 patients divided into three cohorts based on symptomatology: mild (n=24), moderate (n=51), and severe/critical (n=31). Faecal and nasopharyngeal samples were taken, and the microbiota was analyzed. Linear discriminant analysis identified M. salivarium, P. dentalis, and H. parainfluenzae as biomarkers of severe COVID-19 in nasopharyngeal microbiota, while P. bivia and P. timonensis were defined in faecal microbiota. Additionally, a connection between faecal and nasopharyngeal microbiota was identified, with a significant ratio between P. timonensis (faeces) and P. dentalis and M. salivarium (nasopharyngeal) abundances found in critically ill patients. This ratio could serve as a novel prognostic tool for identifying severe COVID-19 cases.

microbiology↗

bioRxiv2024

Prediction of myeloid malignant cells in Fanconi anemia using machine learning

Fanconi anemia (FA) is an inherited bone marrow failure syndrome with cancer predisposition. Most FA patients develop aplastic anemia during childhood and have an extremely high cumulative risk to develop cancer during their lifespan. Myeloid malignancy is one of the main tumor risks for patients with FA, including high-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Although bone marrow transplantation is the treatment of choice for FA patients that develop aplastic anemia, patients with a more stable bone marrow remain at a high risk of presenting MDS/AML and should be monitored for appearance of myeloid malignant clones. Markers for an as-early-as-possible identification of emerging myeloid malignant cells are needed for the monitoring of patients with FA, since quick medical action after detection of neoplastic transformation is needed. In this work we have leveraged publicly available single cell RNA seq (scRNAseq) datasets of patients with MDS and AML for training deep neural networks (DNN). We have generated two machine learning models aimed to identify myeloid malignant transcriptional profiles in scRNAseq datasets from the bone marrow of patients with FA, one for detection of MDS and a second one for AML. Both predictors displayed high sensitivity, specificity, and accuracy for detection of single cell resolution myeloid malignant transcriptional profiles. Multiple tools for analysis of single cell transcriptional data were implemented to characterize the predicted MDS and AML cells. Our analysis suggests that the predicted MDS and AML cells from FA patients are enriched in the lympho-myeloid-primed progenitor (LMPP) and the granulocyte-monocyte progenitor (GMP) populations. The predicted MDS and AML cells have gene expression and master transcriptional factor profiles that suggest malignant transformation and that differ from the rest of FA cells. Also cues of immune evasion were detected using single cell pathway analysis (SCPA) and cell-cell communication profiles. Next work will be aimed to find potential cell surface markers on the predicted MDS and AML cells as well as to assess our predictions in primary samples from FA patients.

cancer biology↗

bioRxiv2023

Unusual Structural Properties of Switchback DNA

Synthetic DNA motifs form the basis of nucleic acid nanotechnology, and their biochemical and biophysical properties determine their applications. Here, we present a detailed characterization of switchback DNA, a globally left-handed structure composed of two parallel DNA strands. Compared to a conventional duplex, switchback DNA shows lower thermodynamic stability and requires higher magnesium concentration for assembly but exhibits enhanced biostability against some nucleases. Strand competition and strand displacement experiments show that component sequences have an absolute preference for duplex complements instead of their switchback partners. Further, we hypothesize a potential role for switchback DNA as an alternate structure in sequences containing short tandem repeats. Together with small molecule binding experiments and cell studies, our results open new avenues for switchback DNA in biology and nanotechnology.

bioengineering↗