RNAapt3D: RNA aptamer 3D-structural modeling database (2023)

Biophysical Journal

Volume 121, Issue 24,

20 December 2022

, Pages 4770-4776

Author links open overlay panel, , , ,


RNA aptamers are oligonucleotides with high binding affinity and specificity for target molecules and are expected to be a new generation of therapeutic molecules and targeted delivery materials. The tertiary structure of RNA molecules and RNA-protein interaction sites are increasingly important as potential targets for new drugs. The pathological mechanisms of diseases must be understood in detail to guide drug design. In developing RNA aptamers as drugs, information about the interaction mechanisms and structures of RNA aptamer-target protein complexes are useful. We constructed a database, RNA aptamer 3D-structural modeling (RNAapt3D), consisting of RNA aptamer data that are potential drug candidates. The database includes RNA sequences and computationally predicted RNA tertiary structures based on secondary structures and implements methods that can be used to predict unknown structures of RNA aptamer-target molecule complexes. RNAapt3D should enable the design of RNA aptamers for target molecules and improve the efficiency and productivity of candidate drug selection. RNAapt3D can be accessed at https://rnaapt3d.medals.jp.

Section snippets


RNA aptamers are expected to be a new generation of biopharmaceutical drugs and drug carriers. Determining the tertiary structures of RNA aptamers and RNA-protein interaction sites are increasingly important because they represent potential targets for new medicines. We introduce the RNA aptamer 3D-structural modeling (RNAapt3D) database, which contains RNA sequences, their secondary and tertiary structures, target proteins of RNA aptamers, and the network of RNA-protein interactions. The

Database content

PDB (https://www.rcsb.org/), PubMed (https://www.ncbi.nlm.nih.gov/pubmed/), Google Scholar (https://scholar.google.com/), and Apta-Index (https://www.aptagen.com/aptamer-index) were used for literature searches to construct the RNAapt3D database. A detailed description of the datasets can be found in Section S1.1. RNAapt3D contains the fields sequence, length, target molecule, adaptation disease, product name, clinical phase, and remark, as well as parameter, structure string, flip position,

RNAapt3D database

We found eight RNA aptamers by a Google search, 31 by a Google Scholar search, five by a Google Patent search, 21 in the PDB, and 29 RNA aptamers from the Apta-Index database. Because some of the RNAs were duplicates, had unknown sequences, or were double-stranded RNA, 55 RNA aptamers were finally identified. The functions of RNA aptamers are strongly dependent on their tertiary structures, and knowing the tertiary structure of an RNA aptamer is crucial in developing the aptamer into an


We constructed the RNAapt3D database, which provides information on RNA sequences, their predicted secondary structure, and predicted tertiary structure models based on the secondary structure(s) using our software and workflow. In the tertiary structure models, the stable RNA aptamer structure and the chemically modified structure were refined by MD simulations. For the RNA sequences that bind to target proteins, the position of the flipped base determined when generating the tertiary

Author contributions

R.S. and K.F. wrote the main manuscript and prepared all figures. K.S. developed the web interface. Y.Y. and A.S. conducted the RNA modeling. All authors reviewed the manuscript. All authors have given approval to the final version of the manuscript.


This work was supported in part by the Life-Science Database Integration Project at the Japan Science and Technology Agency (JST).

Declaration of interests

The authors declare no competing financial interest.

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    What is the difference between DNA Aptamer and RNA Aptamer? ›

    DNA and RNA aptamers are functionally similar but have some differences in their stability and accessibility. Compared with DNA aptamers, RNA aptamers are chemically unstable because of the presence of a reactive hydroxyl group (–OH) at the 2′ position of the ribose sugar in RNA nucleotides.

    What is the disadvantage of RNA Aptamer? ›

    What are the main limitations of aptamers? Aptamers, particularly RNA strands, are prone to quick degradation in biological media due to interactions with biomolecules. Many aptamers have been shown to degrade in blood as quickly as a few minutes, which is far too short for most medical applications.

    Can we do SELEX with RNA? ›

    Aptamers are high-affinity ligands selected from DNA or RNA libraries via SELEX, a repetitive in vitro process of sequential selection and amplification steps. RNA SELEX is more complicated than DNA SELEX because of the additional transcription and reverse transcription steps.

    What is RNA Aptamer? ›

    RNA Aptamers are defined as RNA oligonucleotides that bind to a specific target with high affinity and specificity, similarly to how an antibody binds to an antigen.

    Why are aptamers better? ›

    The use of an aptamer in chromatography has many advantages over the use of an antibody, including an equal or superior affinity and specificity to the target, a smaller size, easier modification and immobilization, better stability, and higher reproducibility.

    What is an aptamer and why we use it? ›

    Aptamers are short, single-stranded oligonucleotides (DNA or RNA) that bind to targets with high affinity and specificity by folding into tertiary structures [7,8]. Aptamers have been extensively used in basic research, to ensure food safety and to monitor the environment.

    Can illumina sequence RNA directly? ›

    RNA-Seq is compatible with all Illumina sequencers. Depending on the library preparation kit, the application, and the data needs, higher or lower throughput sequencers may be more appropriate. Contact your sales representative for more information.

    Is streptavidin an aptamer? ›

    The streptavidin-specific aptamers obtained in this work can be used as tools for characterization of the occupancy of streptavidin-modified surfaces with biotinylated target molecules. The method described in the study is also generally applicable to target molecules other than streptavidin.

    Why can't you do PCR with RNA? ›

    Taq polymerase does not work on RNA samples, so PCR cannot be used to directly amplify RNA molecules. The incorporation of the enzyme reverse transcriptase (RT), however, can be combined with traditional PCR to allow for the amplification of RNA molecules.

    How much does aptamer cost? ›

    Indeed, Aptagen now offer custom aptamers with prices ranging from $1–4 per microgram (for microgram quantities), $300 per gram (for milligram quantities), or even under $50 per gram (for gram quantities)211. Synthesis can be completed in two days or up to two weeks.

    What are the different types of aptamer? ›

    This assay tests the ability of two different types of aptamers (V and I) to detect their respective protein targets (VEGF and IFN-y).

    Can aptamers bind DNA? ›

    Aptamers are small (usually from 20 to 60 nucleotides) single-stranded RN A or DNA oligonucleotides able to bind target molecules with high affinity and specificity.

    Does RNase damage DNA? ›

    RNase A does not degrade DNA but can bind to DNA [25]. If the formation of RNase A-DNA complexes is required for the observed DNA removal, then DNA removal should be inhibited by the presence of excess DNA.

    What are the drawbacks of transcriptomics? ›

    Transcriptomics has been criticized as an inappropriate method to identify genes with large impacts on adaptive responses to the environment because: (1) genes with large impacts on fitness are rare; (2) a large change in gene expression does not necessarily equate to a large effect on fitness; and (3) protein activity ...

    What are the drawbacks of RNA sequencing? ›

    Though RNA-Seq has become a gold standard and can be used as a quantitative assay to determine relative transcript abundance, it is costly, onerous, and employs a time-intensive process for assay design, running the assay and data analysis.

    How do I choose aptamers? ›

    Aptamers can be obtained through an iterative selection process known as SELEX (systematic evolution of ligands by exponential enrichment) by using single-stranded DNA or RNA.

    Are aptamers really promising for diagnostic or therapeutic applications in CVD? ›

    Aptamers can specifically bind to the targets ranging from small molecules to complex structures, making them suitable for a myriad of diagnostic and therapeutic applications.

    Are aptamers natural or synthetic? ›

    Aptamers are short synthetic single-stranded oligonucleotides that specifically bind to various molecular targets such as small molecules, proteins, nucleic acids, and even cells and tissues.

    Are aptamers reusable? ›

    A DNA aptamer is used in the design of an electrochemical ampicillin sensor. The sensor is reagentless and can be reused for three times.

    What is the target of aptamer? ›

    Aptamers are nucleic acid macromolecules that bind to molecular targets, including proteins, with high affinity and specificity.

    What is the difference between an antibody and an aptamer? ›

    They are in general more stable than antibodies, and have a longer shelf life. Aptamers are produced through a simple and inexpensive process and the time required to generate aptamers is comparatively short. Unlike antibodies, aptamers do not need animals or an immune response for their production.

    Can RNA sequencing detect SNPs? ›

    In addition to these applications, RNA-Seq can detect functional genetic variants such as single nucleotide polymorphisms (SNPs), which are restricted to the expressed portion of the genome and represent a large amount of genetic variation in the genome [4, 5].

    How much does RNA sequencing cost? ›

    The cost of RNA-sequencing (RNA-seq) ranges from approximately $36.9 to $173 for a single sample in an mRNA-seq experiment.

    How to make an RNA library? ›

    Libraries are prepared by fragmenting a gDNA or cDNA sample and ligating specialized adapters to both fragment ends. These adapters contain the full complement of sequencing primer hybridization sites. This eliminates the need for additional PCR steps, making the process fully automatable.

    Are aptamers single or double stranded? ›

    Nucleic acid aptamers are single-stranded RNA or DNA oligonucleotides, from 20 to 90 nucleotides.

    Are RNA aptamers more stable? ›

    Native DNA aptamers are more stable than RNA aptamers. The in vitro half-life of an RNA aptamer in plasma is a few seconds, versus 30 to 60 minutes for a DNA aptamer (9–11). RNA in general serves as a transient messenger and is chemically unstable due to a 2' hydroxyl group.

    Do DNA and RNA aptamers exist in cells? ›

    Aptamers are short, single-stranded DNA or RNA (ssDNA or ssRNA) molecules that can selectively bind to a specific target, including proteins, peptides, carbohydrates, small molecules, toxins, and even live cells.

    Is COVID-19 RNA test same as PCR? ›

    The PCR test takes a sample of ribonucleic acid (RNA) and “amplifies” it with the help of lab technologies. Amplifying RNA helps to make even small traces of the COVID-19 virus visible in the test sample. Even if you have a small trace of the virus in your system, the PCR test will detect it.

    How sensitive is COVID RNA PCR? ›

    Analytic Versus Clinical Performance

    The analytic performance of PCR based tests is good, with most assays able to detect 500-5000 copies of viral RNA/mL1 near 100% of the time (analytical sensitivity) and most tests do not cross react with other viruses, so the analytical specificity is near 100% also.

    Can you use RNA as a template for PCR? ›

    RNA template-specific PCR (RS-PCR) is a modification of conventional RNA-PCR in which RNA is reverse-transcribed with a primer that contains at its 5' end a unique nucleotide sequence that may then be exploited in the PCR to amplify preferentially the RNA-derived sequence.

    What are difference between DNA and RNA purification methods? ›

    The key difference between DNA and RNA extraction lies in the pH levels. To extract DNA, the pH required is 8, while for that of RNA extraction, it is 4.7. DNA has a tendency to denature and pass into the organic stage at an acidic pH.

    What is the difference absorbance for DNA and RNA? ›

    The ratio of absorbance at 260 nm and 280 nm is used to assess the purity of DNA and RNA. A ratio of ~1.8 is generally accepted as “pure” for DNA; a ratio of ~2.0 is generally accepted as “pure” for RNA.

    How to design aptamers? ›

    Two major steps exist in aptamer design selection and optimization. In the first step, several polynucleotides with probable binding affinity toward a target are screened by using the SELEX method and then selected. In the second step, aptamers with detected high affinity are shortened, modified, and stabilized.

    What are the 3 types of RNA and how do they differ? ›

    Each of the three types of RNAs performs unique functions and have different structures. mRNA provides a template for gene coding during protein synthesis, tRNA carries the amino acids to the ribosomes, which has to be added to the polypeptide chain and rRNA forms ribosomes along with proteins.

    Why extract RNA instead of DNA? ›

    In short, examining DNA provides us with a static picture of what a cell or organism might do or become, whereas measuring RNA lets us see what a cell/organism is actually doing right now.

    What are the 3 types of RNA and what does each do during translation? ›

    mRNA (messenger RNA): it provides the template for protein synthesis during translation. tRNA (transfer RNA): it brings amino acids and reads the genetic code during translation. rRNA (ribosomal RNA): it plays a structural and catalytic role during translation.

    Can aptamer bind DNA? ›

    Aptamers are small (usually from 20 to 60 nucleotides) single-stranded RN A or DNA oligonucleotides able to bind target molecules with high affinity and specificity.

    What can aptamers bind to? ›

    In the simplest view, aptamers can be thought of as nucleic acid analogs to antibodies. They are able to bind specifically to proteins, and, in many cases, that binding leads to a modulation of protein activity.

    Can Nanodrop distinguish RNA from DNA? ›

    Yes, Nanodrop will not distinguish RNA and DNA. The reading settings just give you corrections for the somewhat different absorbance coefficients. For example, for one OD of RNA, the concentration is 40µg/ml, and DNA is 50µg/ml.

    How do you quantify RNA using a spectrophotometer? ›

    The concentration of RNA isolated with RNeasy Kits can be determined by measuring the absorbance at 260 nm (A260) in a spectrophotometer. Absorbance readings should be greater than 0.15 to ensure significance. An absorbance of 1 unit at 260 nm corresponds to 40 µg of RNA per ml (A260 = 1 = 40 µg/ml).

    How to determine good quality DNA and RNA using spectrophotometer? ›

    To evaluate DNA purity, measure absorbance from 230nm to 320nm to detect other possible contaminants. The most common purity calculation is the ratio of the absorbance at 260nm divided by the reading at 280nm. Good-quality DNA will have an A260/A280 ratio of 1.7–2.0.


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