Nucleotides form the building blocks of life on Earth with all living things built off chains of these chemical structures that encode the genetic instructions carried by DNA. Nucleic acids were first discovered in the mid-1800s by Friedrich Miescher, who was the first to recognize DNA as a distinct molecule separate from the nucleus of a cell. Over the next century, a basic understanding of the chemistry and genetics behind nucleic acids was uncovered, ultimately coming together with the hallmark research of Watson and Crick, who helped to form our modern understanding of the structure of DNA.
Around the same time as Watson and Crick were bringing to light the new world of molecular biology, other researchers began to chemically synthesize their own strands of nucleic acids. Thus, oligonucleotides were formed. From the Greek world oligoi meaning “few” or “small,” oligonucleotides are small, synthetic strands of nucleic acids. The first attempts at synthesis were slow and unstable, relying on H-phosphonate and phosphate triester methods to form oligonucleotides by hand. Today, synthesis of oligonucleotides is largely automated with synthesizer instruments and large-scale production possible through a number of vendors including Thermo Fisher and Danaher.
While oligonucleotides originally referred to short DNA or RNA molecules, many other types of oligonucleotides have been developed. One of the most interesting types developed are antisense oligonucleotides. Like many other types of oligonucleotides, these are single strands of RNA or DNA, but these strands are synthesized to target messenger RNA. These oligonucleotides have the ability to alter mRNA expression through a variety of different mechanisms, which have shown promising therapeutic avenues. Specifically, Morpholino oligonucleotides are used to modify gene expression with some Morpholino-based therapeutics already approved by the FDA to treat Duchenne muscular dystrophy.
Neurodegenerative diseases are another key area of research for antisense oligonucleotide-based therapies. Due to the high degree of specificity, these types of oligonucleotides can target specific RNA sequences that have been linked to diseases like Parkinson’s and Alzheimer’s. Indeed, several recent developments have shown promise for the future alleviation of these diseases. Earlier this summer, researchers at the UC San Diego School of Medicine were studying a protein called PTB, known for binding RNA and influencing what genes are activated in a cell. They used a non-infectious virus carrying an antisense oligonucleotide to inhibit PTB in the midbrain of mice. The treatment led to new neuron growth and the disappearance of Parkinson’s symptoms in the mice.
Another area of relevant disease research lies in COVID-19. With hundreds of different vaccines and treatments currently being developed globally, there is no shortage in the techniques used to inhibit the virus. The SARS-CoV-2 virus is a single-stranded RNA virus whose genome has been mapped out since the early days of the pandemic. Despite this, the specific functions of the genes remain a mystery. Current research looks at antisense oligonucleotides binding to the s2m element in the SARS-CoV-2 virus, as it has been found in all patient samples of the virus and is believed to be not likely to mutate. Research models have shown inhibition of viral replication of modified astroviruses in human cells, showing promise for a similar treatment of the SARS-CoV-2 virus.
While antisense oligonucleotides represent a fascinating and ever-growing research area for oligonucleotides, many other applications exist. An in-depth look at this market and many others, including cell culture products, life science reagents, and chromatography consumables can be found in SDi’s Global Laboratory Consumables 2020 report. This report includes market size estimates as well as forecasts segmented by product type, region, end market, and application. Also included is information of vendor participation and market share.