Complementary Base Pairing Research Articles

Excited-State Intramolecular Proton Transfer-Driven Photon-Gating for Photoelectrochemical Sensing of CO-Releasing Molecule-3.

Different from prevalent approaches such as immunological recognition, complementary base pairing, or enzymatic regulation in current photoelectrochemical (PEC) sensing, this study reported an excited-state intramolecular proton transfer (ESIPT)-driven photon-gating PEC sensor. The sensor is developed for the detection of CO-releasing molecule-3 (CORM-3) by modifying an ESIPT-switched organic fluorescent probe molecule (NDAA) onto the surface of a p-type semiconductor (BiOI). The NDAA can be excited and exhibit strong green fluorescence after responding with CORM-3, resulting in an electrode-interface photon competitive absorption effect due to the switch on ESIPT and considerably reducing the photocurrent signal. The experimental results revealed that the as-developed PEC sensor achieved good analytical performance with high selectivity and sensitivity, with a linear range of 0.01-1000 μM and a lower detection limit of 6.5 nM. This work demonstrates the great potential of the organic fluorescent probe molecule family in advancing PEC analysis. It is anticipated that our findings will stimulate the creation of diverse functional probes possessing distinctive characteristics for inventive PEC sensors.

Scientific Review of the Proarrhythmic Risks of Oligonucleotide Therapeutics: Are Dedicated ICH S7B/E14 Studies Needed for Low-Risk Modalities?

Oligonucleotide therapeutics (ONTs) represent a new modality with unique pharmacological and chemical properties that modulate gene expression with a high degree of target specificity mediated by complementary Watson-Crick base pair hybridization. To date, the proarrhythmic assessment of ONTs has been influenced by International Conference on Harmonization (ICH) E14 and S7B guidance. To document current hERG/QTc evaluation practices, we reviewed US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) Approval Packages (source: PharmaPendium.com) and collated preclinical and clinical studies for 17 marketed ONTs. In addition, clinical QTc data from 12 investigational ONTs were obtained from the literature. Of the marketed ONTs, eight were tested in the hERG assay with no inhibitory effect identified at the top concentration (range: 34-3,000 μM) tested. Fourteen of the ONTs were evaluated in nonhuman primate cardiovascular studies with 11 of them in dedicated telemetry studies. No effect on QTc intervals were observed (at high exposure multiples) in all studies. Clinically, four ONTs were evaluated in TQT studies; an additional six ONTs were assessed by concentration-QTc interval analysis, and six by routine safety electrocardiogram monitoring. None of the clinical studies identified a QTc prolongation risk; the same was true for the 12 investigational ONTs. A search of the FDA Adverse Event Database indicated no association between approved ONTs and proarrhythmias. Overall, the collective weight of evidence from 29 ONTs demonstrate no clinical proarrhythmic risk based on data obtained from ICH S7B/E14 studies. Thus, new ONTs may benefit from reduced testing strategies because they have no proarrhythmic risk, a similar cardiac safety profile as monoclonal antibodies, proteins, and peptides.

“Off-on” signal-switchable electrochemiluminescence aptasensor based on Cu2O-ABEI-AgNPs mediated signal amplification for the detection of profenofos

An “off-on” signal-switchable electrochemiluminescence (ECL) aptasensor was designed for the detection of profenofos based on Cu2O-ABEI-AgNPs as ECL enhancers. Cubic Cu2O was prepared as a core, and AgNO3 was reduced to silver nanoparticles (AgNPs) by N-(4-Aminobutyl)-N-ethylisoluminol (ABEI) as a shell on the Cu2O surface. The Cu2O with a large surface area could enhance the fixation of AgNPs. Cu2O and AgNPs were utilized as catalysts to enhance the double amplification ECL signals. Additionally, a molecular probe consisting of gold nanoparticles (AuNPs), a T-type aptamer (consisting of thymines “T”, referred to as TApt), and aptamer (Apt) was prepared (referred to as AuNPs-Apt-TApt). The presence of mercury ion (Hg2+) could potentially quench the ECL signal and bind the thymine-Hg2+-thymine (T-Hg2+-T) structure. The structure formed a probe with Apt and AuNPs. The complementary short chain of aptamer (CApt) was designed and immobilized on AgNPs. In the absence of profenofos, the Apt and CApt were bound through complementary base pairing. The probe was immobilized on the electrode, resulting in quenching of the signal (switched into “off”). However, upon the presence of profenofos, the probe was detached from the electrode, and the signal was restored (switched into “on”). Finally, the aptasensor had a broad detection range (1 ×10-3 ng/mL∼1 ×102 ng/mL) with a lower limit of detection (LOD, 3 ×10-4 ng/mL) and an excellent recovery rate (94.34%∼113.80%) for the detection of profenofos in vegetables. The aptasensor had good stability, repeatability and specificity.

A controllable Y-shaped DNA structure assisted aptasensor for the simultaneous detection of AFB1 and OTA based on ARGET ATRP.

The development of a simple, rapid, and sensitive technology for the simultaneous detection of mycotoxins is of great significance in ensuring the safety of foods and drugs. Herein, a fluorescence aptasensor with high sensitivity and reproducibility for the simultaneous detection of aflatoxin B1 (AFB1) and ochratoxin A (OTA) was developed. In this sensing system, AFB1 and OTA aptamers were co-immobilized on the surface of magnetic beads (MBs) to form a Y-shaped structure through the principle of complementary base pairing, and were used as recognition probes to specifically capture the target. Activators regenerated by electron transfer for atom transfer radical polymerization (ARGET ATRP) was used as a signal amplification strategy to improve the sensitivity. The initiator modified at the end of an antibody initiates the ARGET ATRP reaction. Different fluorescence signals were designed to achieve the simultaneous detection of OTA and AFB1 with limits of 426.18 and 79.55 fg mL-1 for AFB1 and OTA, respectively. In addition, experiments were conducted on three types of samples, and the recoveries of the two mycotoxins ranged from 87.30% to 109.50%, with relative standard deviations ranging from 0.50% to 4.92% under reproducible conditions. The results suggest that the developed aptasensor is sufficient to meet the different regulatory requirements of the two mycotoxins in food and drug safety and shows great potential.

A novel chemiluminescence sensor for alpha-fetoprotein detection based on an aptamer-luminol modified magnetic graphene oxide and copper-based MOF composite.

Herein, an aptamer-luminol modified magnetic graphene oxide and copper-based MOF composite was prepared and used to build a novel target-triggered "turn on" chemiluminescence (CL) sensor for alpha-fetoprotein (AFP) detection. Magnetic graphene oxide (MGO) was functionalized with the complementary sequence of the AFP aptamer (cDNA), and then MGO-cDNA was linked to aptamer modified luminol (Apt-luminol) through the complementary base pairing effect. The functionalized magnetic graphene oxide (MGO-cDNA/Apt-luminol) was prepared as a specific magnetic separation and signal switch material. ZnONPs-Au@CuMOFs shows excellent catalytic performance and was used as a catalyst for the luminol-H2O2 reaction. AFP will specifically recognize and bind to Apt on MGO-cDNA/Apt-luminol when AFP is present, which causes luminol release and triggers the CL reaction. The released luminol encounters ZnONPs-Au@CuMOFs and produces strong CL intensity. Therefore, a novel target-triggered "turn on" CL method with high selectivity and sensitivity for detecting AFP has been established. The linear range and detection limit were 1.0 × 10-4-50 ng mL-1 and 4.2 × 10-5 ng mL-1, respectively. The sensor also exhibited good selectivity, reproducibility and stability, and was finally used for AFP detection in serum samples.

DNA-modified Prussian blue nanozymes for enhanced electrochemical biosensing.

Prussian blue nanoparticles exhibit the potential to be employed in bioanalytical applications due to their robust stability, peroxidase-like catalytic functionality, straightforward synthesis, and biocompatibility. An efficient approach is presented for the synthesis of nucleic acid-modified Prussian blue nanoparticles (DNA-PBNPs), utilizing nanoparticle porosity to adsorb nucleic acids (polyT). This strategic adsorption leads to the exposure of nucleic acid sequences on the particle surface while retaining catalytic activity. DNA-PBNPs further couple with functional nucleic acid sequences and aptamers through complementary base pairing to act as transducers in biosensors and amplify signal acquisition. Subsequently, we integrated a copper ion-dependent DNAzyme (Cu2+-DNAzyme) and a vascular endothelial growth factor aptamer (VEGF aptamer) onto screen-printed electrodes to serve as recognition elements for analytes. Significantly, our approach leverages DNA-PBNPs as a superior alternative to traditional enzyme-linked antibodies in electrochemical biosensors, thereby enhancing both the efficiency and adaptability of these devices. Our study conclusively demonstrates the application of DNA-PBNPs in two different biosensing paradigms: the sensitive detection of copper ions and vascular endothelial growth factor (VEGF). These results indicate the promising potential of DNA-modified Prussian blue nanoparticles in advancing bioanalytical sensing technologies.

DYNAMICS OF COMPLEMENTARY BASE-PAIRS OF DREW-DICKERSON DODECAMER ON THE MILLIAND MICROSECOND TIME SCALE ACCORDING TO THE DATA OF NUCLEAR SPIN RELAXATION DISPERSION R1ρ OF IMINO PROTONS

Drew-Dickerson Dodecamer (DDD) is one of the well-known DNA duplexes. It has been sufficiently well studied by various structure determination methods and appears to be a standard for developing new experimental techniques and molecular mechanical force fields. For this reason, the information about the dynamics of DDD on different time scales is important for constructing more accurate structural-dynamic models and carrying out molecular dynamics calculations of long-term time trajectories that allow simulation of real processes. In this work, the information on the dynamics of DDD base-pairs on the milli- and microsecond time scale, currently missing from the literature, was obtained by means of imino protons’ nuclear spin relaxation (R1ρ) dispersion. It is shown for all the base-pairs, except for terminal and pre-terminal ones, that any dynamic processes in the range of R1ρ method are not observed up to 300 K, but proceed on a faster time scale. For the pre-terminal GC pair, a pronounced dependence of the relaxation R1ρ on the applied spin-lock field strength is observed, which allowed us to extract the information about the pair closing dynamics using a fast exchange model with highly skewed state populations. These data supplement the information obtained previously on the dynamics of DDD complementary base-pairs by exchange-based water magnetization transfer experiments and provide a more complete view of the processes observed in DDD in relation to base-pair opening-closing.

Endonuclease mimetic activity of laccase with sequence preference following redox potential and interaction of bases

Degradation of lignin, a natural macromolecule, by laccase via substrate radicals has been intensively studied. However, the interactions between laccase and DNA have not been thoroughly elucidated to date. In this report, we demonstrate that laccase has the endonuclease-mimetic activity with the sequence preference. The decay of plasmid and cDNA was observed with atomic force microscopy (AFM), electron paramagnetic resonance (EPR) and DNA sequencing. Concomitantly, ▪ appeared, which produced the DNA lesion. The sequencing results showed that A and AA were the preferred nucleotides flanking the cleaved sites. The hydrogen bonds between complementary base pairs and the base redox potential were responsible for the long-lived charge transfer state within the A-repetitive sequence governing the sequence preference. This discovery implies alternative strategies of surviving the phosphorus stress and resistance to alien DNA in certain species, in which laccase is abundant. These results enrich our understanding of the mechanisms of DNA damage and are important for the interpretation of disease treatment.

Solid-State Nanopores Used for the Detection of DNA Molecules

Solid-state nanopore is crucial in dection of DNA molescules. DNA is made up of two antiparallel strands of polynucleotides. They are joined together by hydrogen bonds between complementary base pairs. The DNA structures are essential for the ability of genetic carrier to control gene expression, promote DNA recombination, and enhance mutagenesis. There are many ways to do DNA testing. Among these methods, nanopore have relatively small size which allows single-molecule detection. It is also less expensive. There are two kinds of nanopores, which are solid-state nanopore and biological nanopore. Solid state nanopore has better capacity to be incorporated into systems and arrays. The channel length and diameter of it can be controlled easily. In addition, its surface properties are also tunable. Therefore, this essay discussed concerning with the different types of nanopore technology: FEB, FIB and wet etching. The mechanism of nanopore was also explained. The existence of nanopores is conducive to a series of research on genes, pharmaceuticals, biology and so on.

A smartphone-assisted portable strategy based on maple leaf-like Au/Cu2S/MoS2 composite for photothermal and colorimetric sensing of cortisol

Herein, we describe a first-time synthesis of a maple leaf-like Au/Cu2S/MoS2 composite (denoted as ACM throughout this paper) with both photothermal and peroxidase (POD) activities. Based on the ACM, we developed a smartphone-assisted portable detection platform for the photothermal and colorimetric dual-mode sensing of cortisol in human saliva. Because of complementary base pairing, the “Y”-type signal-probe (formed by the coincubation of ACM-DNA1 and ACM-DNA2) is fixed on cortisol-specific aptamer-functionalized magnetic beads (MB–Aptcortisol). ​In the presence of target cortisol, MB-Aptcortisol is more likely to combine with cortisol, “Y”-type signal-probes are released, which can oxidize 3,3′,5,5′-tetramethylbenzidine (TMB) to blue oxTMB in the existence of H2O2. Notably, the oxTMB exhibits a distinct photothermal response which, in combination with the photothermal properties of the ACM, achieves transduction and signal amplification of cortisol through a cascade enzyme reaction. The photothermal and colorimetric signals increase with increasing target concentrations. This portable dual-signal sensing platform enables the detection of cortisol in the range of 5–10000 ng/mL, with detection limits of 0.11 and 0.25 ng/mL for photothermal and colorimetric signals, respectively (The reference concentration of cortisol in saliva of healthy people is 1–12 ng/mL in the morning and 0.1–3 ng/mL at night). It is inexpensive, user-friendly, and allows for rapid analysis, rendering it suitable for clinical applications.

Expression of nonmuscle myosin IIC is regulated by non-canonical binding activity of miRNAs

The expression of mechanoresponsive nonmuscle myosin II (NMII)C is found to be inducible during tumor progression, but its mechanism is yet to be explored. Here, we report a group of microRNAs (mmu-miR-200a-5p, mmu-miR-532-3p, mmu-miR-680, and mmu-miR-1901) can significantly repress the expression of nonmuscle myosin IIC (NMIIC). Interestingly, these microRNAs have both canonical and non-canonical binding sites at 3/UTR and coding sequence (CDS) of NMIIC's heavy chain (HC) mRNA. Each of the miRNA downregulates NMHC-IIC to a different degree as assessed by dual-luciferase and immunoblot analyses. When we abolish the complementary base pairing at canonical binding site, mmu-miR-532-3p can still bind at non-canonical binding site and form Argonaute2 (AGO2)-miRNA complex to downregulate the expression of NMIIC. Modulating the expression of NMIIC by miR-532-3p in mouse mammary tumor cells, 4T1, increases its tumorigenic potential both invitro and invivo. Together, these studies provide the functional role of miRNA's non-canonical binding mediated NMIIC regulation in tumor cells.

Small Non-Coding RNAs in Male Reproduction.

Male reproductive functions are strictly regulated in order to maintain sperm production and fertility. All processes are controlled by precise regulation of gene expression, which creates specific gene expression programs for different developmental stages and cell types, and forms the functional basis for the reproductive system. Small non-coding RNAs (sncRNAs) are involved in gene regulation by targeting mRNAs for translational repression and degradation through complementary base pairing to recognize their targets. This review article summarizes the current knowledge on the function of different classes of sncRNAs, in particular microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs), during male germ cell differentiation, with the focus on sncRNAs expressed in the germline. Although transcriptionally inactive, mature spermatozoa contain a complex population of sncRNAs, and we also discuss the recently identified role of sperm sncRNAs in the intergenerational transmission of epigenetic information on father's environmental and lifestyle exposures to offspring. Finally, we summarize the current information on the utility of sncRNAs as potential biomarkers of infertility that may aid in the diagnosis and prediction of outcomes of medically assisted reproduction.

Leveraging QM/MM and Molecular Dynamics Simulations to Decipher the Reaction Mechanism of the Cas9 HNH Domain to Investigate Off-Target Effects.

The clustered regularly interspaced short palindromic repeats (CRISPR) technology is an RNA-guided targeted genome-editing tool using Cas family proteins. Two magnesium-dependent nuclease domains of the Cas9 enzyme, termed HNH and RuvC, are responsible for cleaving the target DNA (t-DNA) and nontarget DNA strands, respectively. The HNH domain is believed to determine the DNA cleavage activity of both endonuclease domains and is sensitive to complementary RNA-DNA base pairing. However, the underlying molecular mechanisms of CRISPR-Cas9, by which it rebukes or accepts mismatches, are poorly understood. Thus, investigation of the structure and dynamics of the catalytic state of Cas9 with either matched or mismatched t-DNA can provide insights into improving its specificity by reducing off-target cleavages. Here, we focus on a recently discovered catalytic-active form of the Streptococcus pyogenes Cas9 (SpCas9) and employ classical molecular dynamics and coupled quantum mechanics/molecular mechanics simulations to study two possible mechanisms of t-DNA cleavage reaction catalyzed by the HNH domain. Moreover, by designing a mismatched t-DNA structure called MM5 (C to G at the fifth position from the protospacer adjacent motif region), the impact of single-guide RNA (sgRNA) and t-DNA complementarity on the catalysis process was investigated. Based on these simulations, our calculated binding affinities, minimum energy paths, and analysis of catalytically important residues provide atomic-level details of the differences between matched and mismatched cleavage reactions. In addition, several residues exhibit significant differences in their catalytic roles for the two studied systems, including K253, K263, R820, K896, and K913.

A double-negative feedback loop between NtrBC and a small RNA rewires nitrogen metabolism in legume symbionts.

Root nodule endosymbioses between diazotrophic rhizobia and legumes provide the largest input of combined N to the biosphere, thus representing an alternative to harmful chemical fertilizers for sustainable crop production. Rhizobia have evolved intricate strategies to coordinate N assimilation for their own benefit with N2 fixation to sustain plant growth. The rhizobial N status is transduced by the NtrBC two-component system, the seemingly ubiquitous form of N signal transduction in Proteobacteria. Here, we show that the regulatory sRNA NfeR1 (nodule formation efficiency RNA) of the alfalfa symbiont Sinorhizobium meliloti is transcribed from a complex promoter repressed by NtrC in a N-dependent manner and feedback silences ntrBC by complementary base-pairing. These findings unveil a more prominent role of NtrC as a transcriptional repressor than hitherto anticipated and a novel RNA-based mechanism for NtrBC regulation. The NtrBC-NfeR1 double-negative feedback loop accurately rewires symbiotic S. meliloti N metabolism and is likely conserved in α-rhizobia.

Exonuclease III‑assisted and target-induced conformational change of DNA hairpins for electrochemical detection of mercury (II)

Here, we report a DNA hairpin strategy for electrochemical determination of Hg2+ based on T-Hg2+-T pairs and exonuclease III (Exo III) assistance. The innovation of this work lies in the designed DNA structure and detection principles. Unlike the previously reported DNA hairpin structure, the ring portion of the hairpin DNA we designed consisting of T bases serves as a recognition probe, forming a T-Hg-T complex with Hg2+. The stem is composed of 5 pairs of complementary bases, which is conducive to the stability of the hairpin structure. After the formation of T-Hg-T in the ring, with the help of Exo III, Exo III can digest more DNA than the T bases designed in the stem. In this event, the shorter the length of the remaining DNA strand on the electrode, the weaker the repulsive force against [Fe(CN)6]3−/4−, and the stronger the differential pulse voltammetry (DPV) current signal, achieving “signal-on” transitions. Under the optimal conditions, the DPV current response increases with increasing Hg2+ concentration and is linear with the logarithm of Hg2+ concentration (1 nM–10 μM). The limit ofdetection is 0.16 nM. The electrochemical sensor was successfully applied to the determination of Hg2+ in river water.

FADH2-mediated radical polymerization amplification for microRNA-21 detection

For early diagnosis of disease, ultrasensitive mircoRNA-21 detection has considerable potential. In this paper, an ultra-sensitive fluorescence detection method for microRNA was developed by atom transfer radical polymerization (ATRP). This ATRP reaction was first initiated by using flavin mononucleotide (FADH2). The DNA probe 1 modified with amino group was fixed on the magnetic nanoparticle Fe3O4, and microRNA-21 was added to form the probe 1-microRNA-21. Another carboxy-modified DNA 2 forms a sandwich structure with the bound microRNA-21. Two terminally modified DNA types are used as microRNA probes, using complementary base pairing to form a stable super-sandwich structure between the DNA probe and the microRNA. Under optimal conditions, microRNA was detected in PBS buffer with a detection limit of 0.19 fM. And even in 10% of human serum, microRNA-21 can be detected with a detection limit of 47.8 fM. Results show that this method has high selectivity, efficiency and stability, which broad application prospect in microRNA ultra-sensitive detection.

Engineering Nucleotidoproteins for Base‐Pairing‐Assisted Cytosolic Delivery and Genome Editing

AbstractProtein therapeutics targeting intracellular machineries hold profound potential for disease treatment, and hence robust cytosolic protein delivery technologies are imperatively demanded. Inspired by the super‐negatively charged, nucleotide‐enriched structure of nucleic acids, adenylated pro‐proteins (A‐proteins) with dramatically enhanced negative surface charges have been engineered for the first time via facile green synthesis. Then, thymidine‐modified polyethyleneimine is developed, which exhibits strong electrostatic attraction, complementary base pairing, and hydrophobic interaction with A‐proteins to form salt‐resistant nanocomplexes with robust cytosolic delivery efficiencies. The acidic endolysosomal environment enables traceless restoration of the A‐proteins and consequently promotes the intracellular release of the native proteins. This strategy shows high efficiency and universality for a variety of proteins with different molecular weights and isoelectric points in mammalian cells. Moreover, it enables highly efficient delivery of CRISPR‐Cas9 ribonucleoproteins targeting fusion oncogene EWSR1‐FLI1, leading to pronounced anti‐tumor efficacy against Ewing sarcoma. This study provides a potent and versatile platform for cytosolic protein delivery and gene editing, and may benefit the development of protein pharmaceuticals.

Engineering Nucleotidoproteins for Base-Pairing-Assisted Cytosolic Delivery and Genome Editing.

Protein therapeutics targeting intracellular machineries hold profound potential for disease treatment, and hence robust cytosolic protein delivery technologies are imperatively demanded. Inspired by the super-negatively charged, nucleotide-enriched structure of nucleic acids, adenylated pro-proteins (A-proteins) with dramatically enhanced negative surface charges have been engineered for the first time via facile green synthesis. Then, thymidine-modified polyethyleneimine is developed, which exhibits strong electrostatic attraction, complementary base pairing, and hydrophobic interaction with A-proteins to form salt-resistant nanocomplexes with robust cytosolic delivery efficiencies. The acidic endolysosomal environment enables traceless restoration of the A-proteins and consequently promotes the intracellular release of the native proteins. This strategy shows high efficiency and universality for a variety of proteins with different molecular weights and isoelectric points in mammalian cells. Moreover, it enables highly efficient delivery of CRISPR-Cas9 ribonucleoproteins targeting fusion oncogene EWSR1-FLI1, leading to pronounced anti-tumor efficacy against Ewing sarcoma. This study provides a potent and versatile platform for cytosolic protein delivery and gene editing, and may benefit the development of protein pharmaceuticals.

Endogenous Enzyme-Activatable Spherical Nucleic Acids for Spatiotemporally Controlled Signal Amplification Molecular Imaging and Combinational Tumor Therapy.

Due to the adjustable hybridization activity, antinuclease digestion stability, and superior endocytosis, spherical nucleic acids (SNAs) have been actively developed as probes for molecular imaging and the development of noninvasive diagnosis and image-guided surgery. However, since highly expressed biomarkers in tumors are not negligible in normal tissues, an inevitable background signal and the inability to precisely release probes at the chosen region remain a challenge for SNAs. Herein, we proposed a rationally designed, endogenous enzyme-activatable functional SNA (Ep-SNA) for spatiotemporally controlled signal amplification molecular imaging and combinational tumor therapy. The self-assembled amphiphilic polymer micelles (SM-ASO), which were obtained by a simple and rapid copper-free strain-promoted azide-alkyne cycloaddition click reaction between dibenzocyclooctyne-modified antisense oligonucleotide and azide-containing aliphatic polymer polylactic acid, were introduced as the core elements of Ep-SNA. This Ep-SNA was then constructed by connecting two apurinic/apyrimidinic (AP) site-containing trailing DNA hairpins, which could occur via a hybridization chain reaction in the presence of low-abundance survivin mRNA to SM-ASO through complementary base pairing. Notably, the AP site-containing trailing DNA hairpins also empowered the SNA with the feasibility of drug delivery. Once this constructed intelligent Ep-SNA nanoprobe was specifically cleaved by the highly expressed cytoplasmic human apurinic/apyrimidinic endonuclease 1 in tumor cells, three key elements (trailing DNA hairpins, antisense oligonucleotide, and doxorubicin) could be released to enable subsequent high-sensitivity survivin mRNA imaging and combinational cancer therapy (gene silencing and chemotherapy). This strategy shows great application prospects of SNAs as a precise platform for the integration of disease diagnosis and treatment and can contribute to basic biomedical research.

Evolution of High-Affinity ssDNA Sequence to Carbon Nanotube

Colloidal ssDNA-wrapped single walled carbon nanotube (ssDNA-SWCNT) has been used as the second near-infrared (NIR-II, 1000 -1700 nm) fluorescent nanoprobes with outstanding biocompatibility, and acts as various optical nano sensors for biological analytes such as a dopamine and serotonin. The stability and affinity of ssDNA on the SWCNT surface significantly depends on the sequence of ssDNA, however the large-scale quantitative analysis between ssDNA sequence library, which has high affinity to the SWCNT surface, was repeatedly selected from a random ssDNA(N30) library (~1018) and the resulting sequence data was analyzed. The binding affinity of ssDNA to SWCNT was quantitatively characterized. To quantitatively analyze the kinetics of the process which occurs solvatochromic shift by sodium cholate, assumed the dynamics follow a first-order kinetic model and fit the experimental data using exponential regression, from which decay time constants were determined. As a result, the highest binding affinity of ssDNA to SWCNT was quantitatively characterized by time constant (1.5 X106 sec) which increased by 100 times compared to the N30 random library. Through analysis of the ssDNA sequences with high affinity for the SWCNT surface, we found that the sequences contain high contents of cytosine and adenine nucleotides and complementary base pairs appeared at distance of 5 to 8 bases. This novel sequence library can be applied for the preparation of the ultra-stable ssDNA-SWCNT dispersion and used for anchoring surface ligands for SWCNT as biosensor. Figure 1