Oligonucleotide Synthesis Oligonucleotide Therapeutics Can be Used to Treat Various Rare Diseases


Oligonucleotide Synthesis
Oligonucleotide Synthesis 


Oligonucleotide synthesis is a chemical process that creates short nucleic acid chains for a variety of applications. These include DNA primers, cloning, and molecular diagnostics. Oligonucleotides are synthesized in a repetitive reaction cycle. Various methods of purification are used depending on the application. Achieving yield objectives is a concern during the synthesis process. However, these processes can be improved by using the real-time spectroscopic monitoring and discriminate modeling. A number of process analytical technologies can be used to achieve yield goals.

Oligonucleotide synthesis begins by linking phosphodiester-linked nucleobases to a solid support. The phosphodiester-linked nucleosides then undergo oxidation. This transforms the phosphite triester linkage to a stable phosphate triester. Once a stable phosphate triester is formed, the new nucleoside is added to the end of the chain. If the supporting nucleoside is not able to react with the new nucleoside, it will be capped with an acetyl group. It is important to protect the supporting oligo from damage during this step.

The global Oligonucleotide Synthesis Market is estimated to be valued at US$ 2,874.1 Million in 2020 and is expected to exhibit a CAGR of 11.3% during the forecast period (2020-2027).

The next step involves de-blocking, a process that removes the specialized protection groups. This protects the solid support-linked nucleosides from polymerization. The free 5' hydroxyl group can then interact with the next nucleoside. De-blocking is done by a special reagent. Next, a series of reactions is performed to further optimize the chemistry. For example, slurry reaction is sometimes used. Another selective reaction is Michael addition. Typically, these reactions involve maleimide derivatives. Alternatively, extendible amidites can be used.

Oligonucleotide sequences are generally produced from 3' to 5'. This length is critical to different applications. Longer sequences may have potential to produce unwanted by-products. Therefore, proper control of the process is essential to achieve the desired yield. The technique is extremely useful in current laboratory practice because it provides a rapid and inexpensive access to custom-made oligonucleotides of the desired sequence. At present, 15 oligonucleotide therapeutics have been approved in the United States to treat various rare diseases and 4 oligonucleotide therapeutics are used to treat Duchenne muscular dystrophy.

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