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This article is adapted from the original, which first appeared on the Twist Bioscience blog.

Oligonucleotides (or oligos for short) are one of the most important tools in modern day molecular biology. Without oligos, today’s biotechnology, diagnostic, and pharmaceutical industries simply couldn’t exist.

What is an Oligo?
To understand what is so special about oligos, we should first answer an important question: What is an oligo?

Oligos are short, synthetic strands of DNA or RNA.

The word oligonucleotide is derived from the Greek word olígoi, meaning “few” or “small”, and nucleotide, which are the building blocks of nucleic acids, such as DNA. Oligos are constructed chemically using an oligo synthesizer, and have advanced broad areas of scientific research and development.

Cutting edge oligos
With a simple reaction, called phosphoramidite chemistry, strings of A, T, C and G, nucleotides can be created in any desired order, one base after another.

While the early methods focused on building short oligonucleotides one at a time, DNA synthesis technology developed at Twist Bioscience can synthesize hundreds of thousands of unique oligonucleotides simultaneously.

Instead of the traditional plastic or glass used as the surface on which to chemically “write” DNA sequences, Twist Bioscience harnesses the properties of silicon to enable synthesis of oligos on a world-leading scale.

Silicon, the 14th element in the periodic table, and the second most abundant element on earth, is most famous for its use in semiconductor microchips in computers. It forms a dense, highly-uniform crystal lattice excellent for engineering on a micro-scale.

Twist Bioscience achieves its high-throughput scale by manufacturing microscopic reaction clusters on silicon plates. These decreased reaction volumes massively increase DNA synthesis capacity, ultimately allowing researchers to access more DNA than ever before while also increasing quality, reducing research time scales, increasing research breadth, and improving cost efficiency of every experiment.

One of the silicon-based plates used by Twist Bioscience to simultaneously synthesize hundreds of thousands of oligos.

Two world-changing applications for oligos.

Application 1: Storing the world’s data for 10,000 years
Possibly the most innovative application for oligonucleotides is in digital data storage!

We are living in the data age, and are in the middle of a data boom. Digital data is commonly stored using silicon wafers in flash storage media, and current estimates suggest that by the year 2040, there will not be enough silicon in the world to store all of the data being generated. However, most stored information will only need to be accessed on rare occasions, so data can be archived on something other than silicon.

Current data archives are stored in banks of magnetic tapes. Unfortunately, tapes are not a sustainable solution, as they are energy intensive, space consuming, and require re-copying every ten years due to degradation.

A robotic tape library for physical data storage (source: Wikicommons, Author: Austin Mills)

collaboration between researchers at Microsoft, Twist Bioscience, and the University of Washington has developed a way to archive digital data in the chemical sequence of DNA. Instead of the binary data (ones and zeros) being stored on tapes, data can be encoded into quaternary data and be stored in DNA as A, T, C and G nucleotides.

DNA is a truly amazing resource for digital data storage. 1 gram of DNA, the size of a small spoonful, could theoretically hold up to one trillion gigabytes of data. DNA also takes up very little physical space and is stable for thousands of years.

We expect many exciting advances in this field in the future. If you are interested in learning more, check out our previous blog post where we discuss the subject at length.

Application 2: High-throughput genome editing with CRISPR
Researchers can study the function of a specific gene by deleting it, and observing what effect this has on a cell or organism. Genes are deleted with genome-editing tools, and a system called CRISPR is currently the most powerful tool for the job.

CRISPR has two parts protein based “nano-scissors” that cut DNA, and an RNA-based guide that tells the scissors exactly where to cut. Each guide is typically less than 100 bases long, so can be encoded by a single synthesized oligo. With this system, a researcher can precisely snip out any part of a cell’s genome, simplifying the genetic research that could lead to cures for difficult to treat genetic diseases like cystic fibrosis and sickle cell anemia.

The three dimensional protein structure of the enzyme Cas9 — the scissors able to cut the DNA as part of the CRISPR system.

CRISPR becomes even more powerful when combined with next generation DNA synthesis. A pool of thousands of CRISPR guides can be produced to delete every gene in a cell’s genome many times over.

This strategy elevates genetic research to a new level. CRISPR and next-generation DNA synthesis now allow researchers to study complex diseases like cancer in more detail than ever before. By deleting all genes in a cell line one by one, previously unknown disease-causing genetic changes can now be studied efficiently. Cell lines can then be produced that replicate these complex diseases, accelerating treatment discovery programs.

Oligos have changed the world
Where would science be today without the oligonucleotide? We would have a difficult time developing new drugs, as oligonucleotides allow us to develop new cell lines for treatment testing. We would also have a poor understanding of many human diseases, many of which we are now able to treat.

Using Twist Bioscience’s silicon-based DNA synthesis technology, it is possible produce more oligos at higher quality than ever before, enabling new applications like DNA data storage. So, to answer the question “What is an oligo?” well, an oligo is a small DNA molecule with a world-changing history and a limitless future!

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