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Oligonucleotides came into focus during the late 20th century, sparked by biologists seeking ways to read and write genetic code. Early pioneers, often working with basic tools compared to what’s around today, laid the groundwork for synthetic DNA and RNA. These days, labs assemble short DNA sequences nearly as easily as baking bread. The technology shifted quickly from manual phosphoramidite chemistry in glass columns to high-throughput automation. Everyone talks about the Human Genome Project, but few mention how early synthetic oligonucleotide methods carried the load for so many landmark experiments. Before PCR took off, researchers used oligonucleotide probes to spot specific DNA snippets in Southern blots, changing the pace of genetic analysis in hospitals and academic centers alike.
Nearly every drug company and genome center stocks oligonucleotides in some form or another. Short, single- or double-stranded chains serve up roles as research primers, molecular beacons, antisense molecules, gene-editing guides, and siRNAs. Most products range from a handful of bases to about 120; orders often arrive lyophilized for stability. Companies offer custom synthesis, so it’s no surprise that oligonucleotides now underlie thousands of applications—much more than a single research area could cover. In the clinic, oligonucleotides drive tests for infectious disease, inherited mutations, and recently stepped into the limelight as therapeutic agents (like in spinal muscular atrophy or rare amyloidosis).
Oligonucleotides build themselves from simple units called nucleotides: a sugar, a phosphate, and one of four bases (A, T/U, C, G). The backbone, held together with sturdy phosphodiester bonds, stays rigid enough for stability yet flexible enough for chemical tweaking. The structure sticks to water, drawing a tight hydration shell; the melting temperature depends on its length, sequence, and any fancy chemical additions. For people who care about purity, contaminants like truncated oligos or salt leftovers stick out as major problems—especially as synthesis scales up. On the bench, the feel, color, and solubility often give clues to quality. DNA and RNA-based oligonucleotides differ slightly: DNA versions handle chillier temps and withstand more storage cycles. With chemical modifications like phosphorothioates or locked nucleic acids, these molecules gain resistance to enzymes and extend their half-life in serum.
Anyone ordering oligonucleotides notices how detailed the paperwork gets. There’s a mandatory list: sequence, length (in nucleotides), mass (in nmol or μg), purity percentage, and any chemical tweaks (like fluorescent labels, quenchers, or backbone modifications). Suppliers often add spectrophotometric readings (A260) and melting temperatures. Lyophilized forms arrive sealed, each tube or plate coded with batch numbers and barcodes for traceability—a nod both to safety and to good manufacturing practices. For research, 99% desalted purity suffices, but clinical work usually needs HPLC or PAGE purification, with certificates outlining each quality step. Some companies now offer pre-mixed primers by plate, complete with dissolving instructions for seamless automation.
The backbone of oligonucleotide preparation starts with solid-phase chemical synthesis. Each base gets linked stepwise on a support (often glass or polystyrene beads) using phosphoramidite chemistry. Reagents like tetrazole jumpstart the addition, and oxidation hardens the bonds. These steps repeat—removing blocking groups and adding the next base—until the full sequence builds up. Afterward, the chain comes off the column in a harsh ammonia bath, followed by desalting, purification, and, in some cases, lyophilization. Automation handles most high-throughput jobs now; liquid handling robots and digital tracking systems keep errors rare. On a research scale, dried oligonucleotides get rehydrated in nuclease-free water and sometimes diluted with TE buffer for long-term storage. Messing with the protocol usually creates less purity or shorter strands, but skilled chemists have squeezed out longer and fancier oligos by slowing the cycles and using cleaner reagents.
It’s hard to overstate the breadth of chemistry on tap with oligonucleotides. Classic DNA comes from natural bases, but endless decorations help them survive enzymes, breach cell membranes, and evade immune systems. Phosphorothioate linkages swap out a non-bridging oxygen for sulfur, shut down nucleases, and give therapies a better shot in blood. Methyl or fluoro groups shore up stability. PEGylation, cholesterol tagging, backbone inversion—each tweak aims for a specific effect. If you walk through a gene therapy lab, you’ll see G-rich oligos shaped into quadruplexes for aptamers, or hairpins stopping transcription. Diagnostic oligonucleotides get labeled with dyes like FAM, HEX, or Cy5 to detect pathogens in qPCR machines. Chemical synthesis pulls off these feat largely because the phosphoramidite method makes it easy to slot in extra building blocks rather than just the plain bases you see in textbooks.
Oligonucleotides get plenty of nicknames depending on their use or slight chemical differences. In the world of gene silencing, you’ll hear “antisense oligonucleotides” or just “ASOs.” In CRISPR work, “guide RNAs” steal the show. Aptamers, morpholinos, locked nucleic acids (LNAs), and peptide nucleic acids (PNAs) go by these specialized names due to backbone tweaks or altered base stacking. Trade names—like Spinraza (nusinersen), Onpattro (patisiran), or Vitravene (fomivirsen)—pop up in FDA paperwork or pharma ads, each anchoring a real therapeutic product that grew up out of academic and industry inventions.
Handling oligonucleotides rarely puts workers at high risk, though carelessness brings issues. Personal experience in wet labs taught me never to treat even “safe” chemicals casually. Good lab practice means gloves, goggles, and clean benches—nucleases from bare skin or dusty air can shred expensive samples before an experiment starts. Storage in cool, dry, protected places, often at -20°C or lower, preserves quality. Even seemingly benign modifications can surprise; some backbone changes led to unexpected inflammatory responses in animal studies, underscoring the need for robust documentation and batch traceability. Quality control stretches from raw material testing to in-process checks and final lot validation, sometimes under Good Manufacturing Practices or ISO standards. For work that touches clinical samples or patient data, regulatory protocols kick in, shaping not just product labeling and shelf-life, but every aspect of shipping and end-user training.
The list of oligonucleotide uses points as much to medical need as to clever innovation. Diagnostics depend on primers and probes, whether to spot COVID-19 in swabs, sequence a cancer hotspot, or detect foodborne pathogens in undercooked meat. Therapeutic oligonucleotides tackle rare diseases like Duchenne muscular dystrophy or spinal muscular atrophy, delivering gene repair in ways small molecules or proteins simply can’t. Cell biology labs, where I spent countless hours, would grind to a halt without primers for PCR, sequencing adapters, or gene-editing guides. Agriculture borrows from these discoveries too, tracking GM crops or detecting viral threats to livestock. Modern forensics matches crime scene DNA with short tandem repeat (STR) analysis, all built on the backbone of custom oligonucleotide synthesis. Pandemic response, cancer care, genetic disease screening—none work without reliable, pure, and customizable oligonucleotides.
Few research areas evolve faster than nucleic acid chemistry. Every year, teams announce new delivery vehicles, chemical tweaks, or ways to dodge off-target toxicity. The science of oligonucleotide therapeutics saw real profits and patient benefit only after decades of setbacks—off-target reactions, kidney toxicity, or immune system flare-ups. These days, more companies blend computational modeling and benchwork. High-throughput screening, advanced structure analysis, and improved preclinical models now spot potential dangers and strengths before molecules enter animals or humans. In my own work, I’ve seen cheap, synthesis-scale automation transform pilot studies; what took weeks in the 2000s now wraps up in days or hours. Funding agencies shape what gets prioritized, with cancer, neurodegeneration, and rare disease commanding the biggest push. Radical advances often come from basic chemistry labs—by switching a chemical group or inventing a stabilizing modification, the field found its way past many roadblocks.
Even game-changing drugs can flop due to toxicity. Oligonucleotides, despite their precision, read like foreign invaders to the immune system. Some modifications extend shelf-life, but they can inflame tissues or trip innate responses—dose-limiting effects that sink plenty of candidates in animal studies. Renal and hepatic effects, thrombocytopenia, and unexpected cytokine release top the list of surprises from clinical trials. Reputable labs run in vitro and in vivo tests—acute, sub-chronic, and chronic—that check organ health, immune activation, and off-target interactions. In one memorable trial, an oligonucleotide with a clever twist raised liver transaminases high enough to halt the program for months. Enhanced safety comes from careful sequence design, chemical caging, and nanoparticle partners that shield or localize payloads. Regulatory agencies demand heavy tox packages, and most companies take feedback seriously, shifting from bench to regulatory filing with hard data in hand.
The oligonucleotide field still feels young, even with its decades-long history. Therapeutic approvals created billion-dollar markets, while artificial intelligence began nudging the design of safer, more stable sequences. The future likely brings orally bioavailable oligos, longer-acting chemistries, and crisper ways to target organs beyond the liver or eye. Advances in nanoparticle carriers and conjugates aim to deliver gene medicines to the right cells, minimizing systemic exposure. In the lab, ever-more affordable synthesis and faster sequencing mean small teams pull off what nationwide centers managed a decade ago. The dream of treating diseases at the level of “spelling errors” in the genome rests on making these tools safer, more predictable, and ever cheaper to produce. As new delivery platforms, editing systems, and chemical inventions arrive, oligonucleotides stand ready to transform medicine and basic biology all over again.
Most people haven’t heard much about oligonucleotides, but these short DNA or RNA fragments have quietly transformed medical science and research over the last few decades. My own first encounter happened in a college genetics lab, pipetting tasteless clear drops that, unknown to me, carried instructions to change living cells. Back then, I didn’t grasp their reach outside the lab bench, but their growing importance catches my attention every year, from news about rare disease treatments to the promise of individualized medicine.
Oligonucleotides form the backbone of many new genetic therapies. New drugs like nusinersen give hope to kids with spinal muscular atrophy, who once faced inevitable progression. Nusinersen works by adjusting how the body reads a gene, thanks to the custom-built nature of these molecules. About a dozen therapies like this earn approval worldwide, and hundreds more enter clinical trials. For parents watching their children regain muscle movement or adults living longer with fewer symptoms, the value of these treatments moves beyond scientific data to everyday hopes and realities.
Every time you hear about PCR tests for COVID-19, oligonucleotides are quietly involved. These fragments direct the testing reaction to the right viral target, making diagnosis possible within hours. In daily life, accurate and fast results shape decisions for millions, whether returning to work, visiting grandparents, or seeking medical care. False negatives and inaccurate results fall through the cracks when the design of oligonucleotides lacks precision, so behind each test, experienced scientists measure accuracy in every detail.
Beyond life-or-death medicine, labs big and small use oligonucleotides to answer questions about everything from seed genetics to cancer resistance. Gene editing tools like CRISPR rely on them for accuracy. These molecules make it possible to design experiments quickly, drive down costs, and improve reproducibility. In my own experience, a single order—just a tiny tube by FedEx—can jumpstart a new project, opening doors to discoveries without months of setup.
Production still costs a lot, especially for complex or custom oligonucleotides. Price tags can limit who gets access, cutting off innovation to only well-funded labs or wealthy healthcare systems. Open science communities push prices lower by sharing synthesis techniques and pooling demand. Growth in manufacturing competition might lower costs for rare disease patients and researchers in developing countries, but industry transparency and fair pricing need pressure from hospitals and advocacy groups.
As with powerful tools, safety isn’t just a regulatory box to check. Off-target effects mean unexpected gene changes, and nobody wants a treatment to fix one problem and cause another. The most experienced geneticists work through long fields of data, testing for any sign of trouble before a new drug leaves the lab. Patients and doctors need clear information to make informed choices, so research journals share not just good news but honest results, missteps, and side effects.
Oligonucleotides thrive where researchers, doctors, and patient advocates talk to each other, sharing lessons learned and mistakes made. Lives improve most when advances leave the academic press and reach the clinic or the bedside. Investment in education for both professionals and patients encourages smarter use and better outcomes. Working together, progress turns scientific promise into changed lives. That’s what continues to make oligonucleotides matter beyond any single discovery.
Oligonucleotides play a quiet but heavy-duty role in labs working on anything from basic genetics to cutting-edge therapies. When researchers need a very specific string of DNA or RNA letters, they don’t order it from nature—they turn to chemical synthesis. Getting these biological building blocks isn’t like baking a loaf of banana bread, but it’s safe to say that the basic process shows how science keeps pushing boundaries.
My time in biotech involved waiting for oligo deliveries as if Christmas morning. Making them comes down to an elegant bit of chemistry on a solid support such as controlled pore glass or polystyrene beads. It starts with a single, tiny anchor. A technician or automated machine adds nucleotides—A, T, G, and C for DNA or A, U, G, and C for RNA—one letter at a time. The order matches whatever genetic trick a scientist is hoping to pull off.
Chemical synthesis relies on what’s called the phosphoramidite method. Each new nucleotide goes through a series of chemical reactions: attachment, oxidation, and then a wash to remove leftovers before the next letter joins the chain. Mistakes can slip in, but with tight controls and purification processes, most oligonucleotides match the requested sequence.
Every step comes with a risk for mistakes, especially if the strand grows too long. In most cases, practical synthetic oligos stay under 200 bases to avoid too many errors crowding the final product. That’s part of why gene synthesis in industry has a certain upper limit before scientists reach for other methods like ligation or enzyme-based assembly.
Impurities ruin experiments. In medical applications, they could even put patients at risk. Labs use high-performance liquid chromatography (HPLC) or polyacrylamide gel electrophoresis (PAGE) to pull out products that match the intended sequence and length. These processes aren’t shortcuts—they’re safeguards that keep everything from a simple PCR reaction to a gene therapy trial from going sideways.
One lesson learned after watching a dozen failed PCRs explode my timeline: Not all vendors deliver equal purity. Researchers compare labs, not out of brand loyalty, but because outcome reliability depends on careful synthesis and clean-up. Major manufacturers share their QC data, but running a quick check with a mass spectrometer in-house can make all the difference when experiments matter.
Prices have dropped over the past decade, making oligo-driven diagnostics and therapies more accessible. Big players scale up custom synthesis, offering turnaround times that seemed wild just a few years ago. Automation has brought consistency, but folks on the ground know that operator judgment—knowing what good looks like—still guides the best results.
Better enzymes and smarter machines already help the process along. There’s constant tinkering to reduce error rates, use greener chemicals, and build longer strands without running up against purity issues. If you’ve worked next to an oligo synthesizer humming through the night, you know the blend of patience, planning, and quality control defines this corner of molecular biology.
DNA and RNA oligonucleotides sound complicated, but both play starring roles in today’s medical breakthroughs. DNA oligos, as short strands of deoxyribonucleic acid, serve as primers for PCR, gene synthesis, and countless diagnostic tests. RNA oligos, their ribonucleic acid cousins, frequently drive gene silencing in research or vaccines like those for COVID-19.
DNA’s backbone contains deoxyribose; RNA’s has ribose—the difference lies in a single oxygen atom. That little switch brings big changes. DNA handles harsh conditions and resists breakdown. RNA tends to fall apart around water and enzymes in a lab. With hands-on experience running PCR, lost samples usually meant mixing up RNA with DNA reagents, or skipping steps to protect fragile RNA.
Another key point: RNA swaps out thymine for uracil. Lab notes fill up with “T” for DNA, but those suddenly read “U” in RNA protocols. This switch affects how synthetic oligos recognize and bind to their targets. The world saw this in vaccine development, where careful tweaking of RNA letters helps keep instructions clear to human cells without running into trouble with the immune system.
Researchers lean on DNA oligonucleotides for tasks that need reliability. Whether designing genetic tests for inherited diseases or pinpointing pathogens, DNA oligos offer flexibility with modifications such as fluorescent tags or biotin. My time setting up university labs drove home how DNA oligos could handle shipping delays or room-temperature storage without falling apart—not true for RNA, which demanded fresh ice and overnight delivery.
RNA oligonucleotides remain more expensive to make and trickier to handle, but they’re irreplaceable where precise gene silencing or rapid mRNA translation is needed. In news reports covering COVID-19 vaccinations, mRNA sequences made the vaccines possible. Chemical changes—like adding methyl groups—helped vaccines stick around longer inside the body, showing how scientists work around RNA’s instability.
Because DNA templates copy pretty easily, DNA oligos crop up in everything from cloning research to criminal forensics, supporting fields well outside core genetics. Ordering RNA oligonucleotides takes extra care: one stray RNase and the sample turns to mush. Suppliers often ship RNA lyophilized and tucked into armored vials with ice packs, versus DNA’s plain packaging. Keeping RNA safe requires dedicated tools and clean, enzyme-free workspaces, which doesn’t always happen in underfunded school or field labs.
Demand for both types of oligonucleotides keeps climbing as gene therapies and precision medicine move into regular treatment. Improved chemical modifications make both DNA and RNA oligos more stable, driving down costs for routine lab work and patient care. Academic and commercial labs now routinely automate oligo synthesis, tracking every order for quality using mass spectrometry or HPLC, helping to keep mistakes out of research and diagnostics.
DNA and RNA oligonucleotides look similar on paper, but their strength and sensitivity, ease of use, and application contexts remain distinct. Careful handling, advanced synthesis, and attention to detail remain crucial as healthcare and research stake more on these deceptively small strands.
Oligonucleotides don’t last forever on a lab bench, and everybody who’s handled precious samples knows how painful it feels to discover a degraded batch after weeks of work. These short DNA or RNA fragments play a centerpiece role in PCR, CRISPR, diagnostics, and so many other molecular biology tools. Poor storage chips away at reliability, drains budgets, and burns time. I’ve seen researchers scramble to repeat experiments because someone skipped over the basics—low temperature, right buffer, protection from light. The science may seem complicated, but the fundamentals for keeping an oligo batch in peak condition follow a few common-sense rules.
Most oligonucleotides hit the lab as dry powders or in solution. Dry stocks usually stand up to -20°C storage without any headaches. If you keep tubes tightly sealed, they stay viable for years. Repeatedly opening and closing tubes leads to condensation and introduces contaminants. It’s easy to forget a tube on the bench as you set up a reaction, yet a short exposure to room temperature rarely spells disaster. Stretching it into days or weeks, though, definitely opens the door for trouble.
In solution, these molecules grow more sensitive. Most protocols recommend storing short-term stocks at 4°C, using nuclease-free water or TE buffer. Longer term, I always reach for the -20°C or -80°C freezer. It’s true that buffer choice makes a difference — water alone leaves samples more fragile, and low-pH or unbuffered solutions chip away at sequence integrity. EDTA in TE buffer helps by tying up metals and keeping nucleases quiet.
Every time oligos thaw and refreeze, they face stress. Even without obvious contamination, each freeze-thaw cracks the DNA or RNA a little more. This damages fragile ends and sometimes causes subtle sequence changes. In my own work, keeping a master stock untouched and drawing smaller aliquots for day-to-day use solved the problem. Single-use aliquots in small volumes mean tubes only defrost once, which beats having to order another batch.
Light—especially UV—acts slowly but surely, especially for dyed or labeled oligonucleotides. A paper towel draped over the sample box or an opaque container buys peace of mind. Glass and plastic both work as long as caps seal tightly.
Dust, bacteria, and bare hands may not seem threatening, but even a fingerprint can introduce nucleases. Gloves and pipette tips clean up most risks. I’ve learned the hard way to never grab a pipette with a snack in the other hand.
Dry oligos do best away from air and humidity. Moist air leads to clumping, and once that happens, dissolving the sample evenly turns into a chore. Silica gel packs or simple desiccators keep the environment dry enough for long-term storage.
Most labs juggle many projects, and mistakes stem from everyday chaos as much as bad intent. I pushed to label vials with date and concentration, and these tiny habits saved colleagues from silent mix-ups. Digital inventory helps but can’t replace good physical habits.
Manufacturers and journals publish guidance, but real progress grows from habits and peer learning. Establishing a routine—tight seals, clear labels, organized freezers, minimal freeze-thaw—pays off over time. Even old-timers in the lab run into issues when they let busy days erode careful storage habits.
Labs that rely on oligonucleotides—short sequences of DNA or RNA—know fresh material can make or break an experiment. Years back, I worked in a lab where we’d find stray tubes of primers in forgotten freezer corners. Some worked, some didn’t, and reordering cost time and money. If you ask researchers about shelf life, you’ll get a story about surprises in PCR, hesitant results, and sometimes compromised data sets.
Lyophilized oligos, meaning dried powder form, keep the longest. Once the synthesis is done and the lab receives that small tube, storing it in a freezer at -20°C holds them in pretty good shape for 18 to 24 months, sometimes even longer. Studies show that these dried oligos resist molecular breakdown remarkably well, thanks to the absence of water. But open the tube too often, let moisture get in, and they’ll start to degrade.
For oligos already dissolved in buffer or water, the clock ticks faster. Solutions stored at -20°C should last several months, up to a year, before the risk of breakdown or contamination rises. Just don’t leave them at room temperature for long. I’ve seen PCR primers lose performance in a matter of weeks left on a bench, especially if exposed to sunlight or heat. Enzymatic activity or nucleases, even in trace amounts, will eventually cut those fragile strands.
Every freeze-thaw cycle stresses the oligo backbone. Each time a tube is taken out, used, and put back, the risk of strand scission grows. Some teams minimize this by making small working aliquots rather than using the master stock every day. It’s a simple habit that saves disappointment, especially in projects with limited budgets or precious samples.
Synthetic purity and modifications matter, too. High-purity oligonucleotides (HPLC- or PAGE-purified) tend to stick around longer, especially if they carry chemical modifications that block degradation. Unmodified, crude-synthesis primers are more finicky—they might not make it as far past the 6-12 month mark in solution, especially with repeated use.
Reputable molecular biology labs keep close watch on oligo inventories and track ordering dates in digital lab notebooks. They adopt simple tracks: pack everything in desiccators or -20°C freezers, and revisit any tube older than a year. Some groups test old stocks on gel runs before risking valuable samples on a big experiment. For clinical labs or high-throughput pipelines, quality managers may enforce strict cutoffs.
At the manufacturer’s side, most suppliers stamp expiry dates based on detailed degradation studies. But in everyday settings, the best guide remains physical integrity—crisp bands on a gel or a strong signal in PCR readouts.
Aliquoting on first use and limiting open times extend the utility of each batch. Buying only what gets used within a year keeps standards high. For long-term archiving, storage in tightly sealed tubes with desiccant pouches or even in ultra-cold conditions ensures less loss by the time that crucial project rolls around.
A bit of vigilance goes far. That keeps the next set of results true and saves the hassle of rescue protocols or costly reorders. In many labs, a culture of careful storage turns up as reliable, reproducible experiments.
| Names | |
| Preferred IUPAC name | oligonucleotide |
| Other names |
Oligonucleotides Oligos |
| Pronunciation | /ˌɒl.ɪ.goʊˈnuː.kli.əˌtaɪdz/ |
| Identifiers | |
| CAS Number | 9009-49-0 |
| Beilstein Reference | 3069075 |
| ChEBI | CHEBI:7754 |
| ChEMBL | CHEMBL1201869 |
| ChemSpider | No ChemSpider ID exists for the product 'Oligonucleotides'. |
| DrugBank | DB06144 |
| ECHA InfoCard | Just the string you requested: "03b334df-2324-43a2-bef9-65457aa94252 |
| EC Number | EC 2.7.7.65 |
| Gmelin Reference | 151828 |
| KEGG | map04130 |
| MeSH | D010046 |
| PubChem CID | 444041 |
| RTECS number | VN2083000 |
| UNII | F5TD010360 |
| UN number | UN 3245 |
| CompTox Dashboard (EPA) | Oligonucleotides |
| Properties | |
| Chemical formula | (C10H12N5O6P)n |
| Molar mass | NaN |
| Appearance | White to off-white powder |
| Odor | Odorless |
| Density | 1.7 g/cm³ |
| Solubility in water | Soluble |
| log P | -4.21 |
| Vapor pressure | Negligible |
| Acidity (pKa) | pKa ~1-2 (phosphate backbone) |
| Basicity (pKb) | 6.0–7.0 |
| Magnetic susceptibility (χ) | −21.7 × 10⁻⁶ |
| Refractive index (nD) | 1.350 |
| Viscosity | Low to medium |
| Thermochemistry | |
| Std molar entropy (S⦵298) | 449.2 J·mol⁻¹·K⁻¹ |
| Pharmacology | |
| ATC code | B02BX10 |
| Hazards | |
| Main hazards | No known significant effects or critical hazards. |
| GHS labelling | Not classified as hazardous according to GHS. |
| Pictograms | GHS07 |
| Signal word | Warning |
| Hazard statements | Not a hazardous substance or mixture according to Regulation (EC) No. 1272/2008. |
| Precautionary statements | Refer to SDS for proper handling and disposal. Wear protective gloves, clothing, and eye protection. Avoid breathing dust or vapors. Wash thoroughly after handling. In case of contact with eyes or skin, rinse immediately with plenty of water. |
| LD50 (median dose) | >2000 mg/kg (rat) |
| PEL (Permissible) | Not established |
| REL (Recommended) | 0.05 mg/m³ |
| Related compounds | |
| Related compounds |
Phosphoramidites Nucleoside triphosphates (NTPs) Locked nucleic acids (LNAs) Morpholino oligos Peptide nucleic acids (PNAs) Aptamers Antisense oligonucleotides siRNA DNA/RNA probes CRISPR guide RNAs |
