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DNA and Nucleic Acid Chemistry
Research Guide
What is DNA and Nucleic Acid Chemistry?
DNA and nucleic acid chemistry is the study of the structure, properties, reactions, and biological functions of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), including techniques for their isolation, labeling, folding prediction, and computational simulation.
This field encompasses foundational methods for nucleic acid manipulation, such as Southern blotting for sequence detection, nick translation for radiolabeling, and guanidinium thiocyanate extraction for RNase-rich tissues. Computational tools like the mfold web server predict nucleic acid secondary structures, while force fields such as GAFF and AMBER enable simulations of proteins, nucleic acids, and organic molecules. The cluster includes 148,918 works focused on G-quadruplex DNA structure, telomeres, therapeutic targets, and antisense oligonucleotides.
Topic Hierarchy
Research Sub-Topics
G-Quadruplex Structure and Stability
Researchers characterize topologies, loop motifs, and cation-dependent folding of intramolecular and intermolecular G4s using NMR, X-ray crystallography, and CD spectroscopy. Computational models predict thermal stability.
Telomeric G-Quadruplexes
Studies focus on human telomeric G4 formation, telomerase inhibition, and shelterin protein interactions at chromosome ends. Cellular imaging tracks G4 dynamics during replication and aging.
G-Quadruplex Ligands Drug Design
Medicinal chemists screen and optimize small molecules, porphyrins, and macrocycles for G4 vs. duplex selectivity. SAR studies correlate binding affinity with antiproliferative activity.
Genomic G-Quadruplexes
Bioinformatics maps potential G4 motifs (PQS) across genomes, validated by sequencing and ChIP. Functional assays link G4s to replication stress, fragility, and transcription pausing.
G-Quadruplex Molecular Recognition
Biophysical studies elucidate protein-DNA interactions with G4s, including helicases (BLM, WRN), transcription factors, and nucleases. FRET and SPR quantify binding kinetics.
Why It Matters
DNA and nucleic acid chemistry underpins molecular biology techniques used in genomics, cancer research, and drug development. Southern (1975) introduced gel electrophoresis for detecting specific DNA sequences, enabling Southern blotting with 32,814 citations and applications in gene mapping. Feinberg and Vogelstein (1983) developed high-specific-activity radiolabeling of DNA fragments, cited 25,150 times, facilitating sensitive hybridization assays in diagnostics. Chirgwin et al. (1979) provided RNA isolation from RNase-rich sources like rat pancreas using guanidinium thiocyanate, cited 22,203 times, supporting gene expression studies. Recent efforts include Ansa Biotechnologies' enzymatic DNA synthesis for ultra-long products and novel enzymatic DNA vaccines achieving comparable immune responses to plasmids, as in SARS-CoV-2 and cancer immunotherapy applications.
Reading Guide
Where to Start
"Detection of specific sequences among DNA fragments separated by gel electrophoresis" by E.M. Southern (1975) – this foundational paper introduces Southern blotting, a core technique for DNA analysis with 32,814 citations, accessible for understanding basic nucleic acid detection.
Key Papers Explained
Southern (1975) established DNA sequence detection via gel electrophoresis, foundational for later labeling methods like Feinberg and Vogelstein (1983), who achieved high-specific-activity radiolabeling of fragments, and Rigby et al. (1977) with nick translation. Chirgwin et al. (1979) extended isolation techniques to RNA from RNase-rich tissues, complementing Marmur (1961) DNA extraction from microorganisms. Zuker (2003) built computational prediction atop these, while Wang et al. (2004) GAFF and Cornell et al. (1995) force fields enable structural simulations of nucleic acids.
Paper Timeline
Most-cited paper highlighted in red. Papers ordered chronologically.
Advanced Directions
Recent preprints emphasize molecular bioengineering of functional nucleic acids for DNA machines and programming via base pairing into 3D conformations. Nucleic Acids Research invites reviews on DNA/RNA function and protein interactions; ACS Chemical Biology covers nucleic acid chemical modifications (73 papers). News highlights Ansa Biotechnologies' enzymatic synthesis for ultra-long DNA and £917,000 funding for nucleic acid networks.
Papers at a Glance
In the News
HitGen Receives New Funding to Discover Novel ...
1. News 2. **Press Release** # HitGen Receives New Funding to Discover Novel Therapeutics for Underserved Diseases Release Time：2025-11-20
Ansa Biotechnologies Targets Nucleic Acid Synthesis ...
Enzymatic DNA synthesis company Ansa Biotechnologies hopes to win a slice of the nucleic acid synthesis market with ultra-long DNA products that it believes are hard to obtain with traditional phos...
New University of Portsmouth led network to fast-track ...
- £917,000 will be spent on maximising the power of nucleic acids such as DNA and RNA
Foundational Projects | Cycle 2 | D2R | DNA to RNA
# Foundational Projects \| Cycle 2 The Foundational Projects funding program supports high-risk, early-stage projects with the potential to be game-changers in the fields of D2R’s areas of interest.
Novel enzymatic DNA produced from a text file achieves comparable immune responses as plasmid vaccine
DNA vaccines have garnered considerable attention due to their recent success in humans for SARS-CoV-2 and immunotherapy for cancer. However, conventional methods for creating and manufacturing DNA...
Code & Tools
This project is in active development, so expect the API to change frequently. JAX-DNA is a Python package for simulating and fitting coarse-graine...
gReLU is a python library to train, interpret, and apply deep learning models to DNA sequences. genentech.github.io/gReLU/ ### License MIT license
**Nuskell** is a compiler framework to translate formal chemical reaction networks (CRNs) into domain-level strand displacement (DSD) systems. To s...
Piperine is a software tool for the automated design of DNA molecules that mimic abstract chemical reaction networks (CRNs) in a test tube.
Multistrand is a nucleic acids kinetic simulator, and is developed by the Winfree group at the California Institute of Technology in Pasadena, Cali...
Recent Preprints
Nucleic Acids Research | Oxford Academic
Critical Reviews and Perspectives are dedicated to reviews relevant to the journal's core areas of interest in DNA/RNA function and the structure and interactions of proteins involved in nucleic ac...
ACS Chemical Biology Journal
- Biology and biological chemistry - Biochemistry - Peptides and proteins (3806) - Lipids (204) - Chemical modification (200) - Precursors (73) - Nucleic acids (73) - Protein dynamics...
Nucleic acids articles from across Nature Portfolio
Nucleic acids (DNA or RNA) are polymers of nucleotides –each nucleotide consists of a pentose sugar, a phosphate group and one of the nitrogenous bases (purines and pyrimidines). Nucleic acids func...
DNA and RNA articles from across Nature Portfolio
DNA and RNA are nucleic acids found in the nucleus of the cells in every living organism. Both nucleic acids participate in the coding, decoding, regulation and expression of genes. ## Latest Resea...
Molecular bioengineering of functional nucleic acids
Nucleic acids (DNA and RNA) are fundamental to life, encoding biological information through linear sequences of nucleotides. Single-stranded nucleic acids, driven by complementary base pairing, fo...
Latest Developments
Recent developments in DNA and nucleic acid chemistry include the design of hypercompact RNA degraders using engineered toxins and Cas6-CBS systems, as well as the expansion of the genetic alphabet to create six-letter DNA with increased structural and chemical diversity for high-affinity aptamers, as of December 2025 (nature.com, nature.com). Additionally, advances include site-specific DNA insertion using engineered recombinases and highly efficient C8–H alkylation of guanine nucleosides via photo-mediated Minisci reactions, with potential applications in disease treatment and diagnostics, as of early 2026 (nature.com, nature.com).
Sources
Frequently Asked Questions
What is the mfold web server used for?
The mfold web server predicts secondary structures of single-stranded nucleic acids, providing easy WWW access for RNA and DNA folding and hybridization prediction. Michael Zuker (2003) developed it for applications in nucleic acid research, with 13,345 citations.
How is RNA isolated from tissues rich in ribonuclease?
Intact RNA is prepared by homogenization in 4 M guanidinium thiocyanate plus 0.1 M 2-mercaptoethanol to denature proteins and break disulfide bonds. Chirgwin et al. (1979) isolated RNA free of protein from rat pancreas, cited 22,203 times.
What are GAFF and AMBER force fields in nucleic acid simulations?
GAFF is a general Amber force field for organic molecules compatible with protein and nucleic acid force fields, covering H, C, N, O, S, P, and halogens. Wang et al. (2004) developed it with 18,623 citations; Cornell et al. (1995) introduced a second-generation force field for proteins, nucleic acids, and organics, cited 13,034 times.
What techniques label DNA to high specific activity?
Nick translation with DNA polymerase I labels DNA in vitro to high specific activity. Rigby et al. (1977) described this method, cited 11,657 times; Feinberg and Vogelstein (1983) advanced radiolabeling of restriction fragments, cited 25,150 times.
How are G-quadruplexes relevant in this field?
G-quadruplex DNA structures are studied for their topology, telomere roles, genomic stability, and as therapeutic targets in cancer via drug design and antisense oligonucleotides. The cluster of 148,918 papers explores their biological functions and molecular recognition.
What is the role of tools like Nuskell in nucleic acid chemistry?
Nuskell compiles formal chemical reaction networks into domain-level strand displacement systems for DNA nanotechnology. It supports diverse CRN-to-DSD translation methods for designing nucleic acid-based computational systems.
Open Research Questions
- ? How can G-quadruplex structures in telomeres be selectively targeted for cancer therapeutics while preserving genomic stability?
- ? What improvements in force field accuracy are needed for simulating G-quadruplex dynamics and protein-nucleic acid interactions?
- ? How do antisense oligonucleotides interact with G-quadruplex motifs to modulate gene expression?
- ? What are the precise roles of G-quadruplexes in molecular recognition and biological functions beyond telomeres?
- ? Can enzymatic DNA synthesis methods scale to produce ultra-long therapeutic nucleic acids matching chemical synthesis fidelity?
Recent Trends
Ansa Biotechnologies advances enzymatic DNA synthesis for ultra-long products challenging phosphoramidite methods.
2025University of Portsmouth leads £917,000 network to accelerate nucleic acid applications like DNA/RNA.
2025Enzymatic DNA from text files matches plasmid vaccine immune responses for SARS-CoV-2 and cancer.
2025Tools like jax-dna for differentiable nucleic acid dynamics and gReLU for deep learning on DNA sequences are in active development.
Preprints focus on programming DNA machines and functional nucleic acid bioengineering .
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