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Phosphorothioate Modification

Oligonucleotide-based therapeutics, such as antisense oligonucleotides (ASOs), are a class of biopharmaceutical products that are designed to alter the expression of target genes in the body. These oligonucleotides provide great potential for the treatment of genetic diseases. In general, oligonucleotides are synthesized as unmodified phosphodiester oligos. But these unmodified oligonucleotides are unstable and easily degraded by nuclease. Phosphorothioate backbone modification is required to reduce nucleolytic degradation. Creative Biolabs is a world-leading custom oligo synthesis service provider who is engaged in offering the best services of oligos synthesis incorporated with phosphorothioate bonds. Aided by our high-quality services, you can obtain more stable oligonucleotides to promote their applications.

Introduction of Phosphorothioate Modification

Phosphorothioate modification is a well-known DNA backbone modification, in which the nonbridging oxygen in the phosphate moiety of the DNA sugar-phosphate backbone is replaced by sulfur. This modification alters the overall chemical properties of oligonucleotides, making them more stable and resistant to nuclease degradation as well as effectively increasing their half-life in serum and cells. Phosphorothioate modification plays an important role in the synthesis of ASOs and small interfering RNA (siRNA). Phosphorothioate bonds are usually introduced into ASOs or siRNAs to increase their nuclease resistance. For example, the modification of 3’-ends or 5’-ends of oligo with phosphorothioate linkages can increase their 3’ or 5’ exonucleases resistance. Thus, today the majority of therapeutic oligonucleotides contain phosphorothioate linkages.

Chemical structure of a phosphorothioate (A) and a phosphorothiolate (B) linkage. Figure 1. Chemical structure of a phosphorothioate (A) and a phosphorothioate (B) linkage. (Islam, 2016)

Why Are Phosphorothioate Bonds Preferred?

Our Services

Our professional expert staff has engaged in oligonucleotide synthesis and phosphorothioate modification for many years and accumulated extensive experience in this filed. According to your special requirements, we can provide a full range of flexible and reliable solutions for therapeutic oligonucleotide synthesis and phosphorothioate modifications.


When you choose custom oligonucleotide modification service at Creative Biolabs, you not only get high-quality custom oligonucleotide production with phosphorothioate modification but also get in-depth scientific support from experts with years of oligonucleotide synthesis experience. If you are interested in our services, please feel free to contact us for more details.


  1. Islam, M.A.; et al. (2016). In vitro and in vivo biophysical properties of oligonucleotides containing 5'-thio nucleosides. Drug discoveries & therapeutics. 10(5):263-270.

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