There are many different strategies and chemical modifications to improve the stability of aptamers. Among these modifications, 2’-fluoro or 2’-O-methyl substitution and 3’ inverted thymidine are commonly used chemical modification strategies to resist nuclease degradation of aptamers.
Background of 3’ Inverted Thymidine Modified Aptamer
Aptamers are selected in buffer systems and are constructed from four natural DNA or RNA bases that are easily degraded by nuclease. Although there are various incomparable advantages, the application of aptamer in organism is still limited. This is because the conformation of aptamers changes easily in different environments, and the small size and molecular weight of aptamers enable them to be rapidly removed through the kidney. In order to overcome these problems, many efforts have been made to design aptamers with enhanced bioavailability.
The first method proposed is to chemically modify different parts of the aptamer to produce nuclease-resistant oligonucleotides. An important set of modifications are made at the 3’-end or 5’-end of the aptamer. Adding an inverted thymidine to the 3’ end of the aptamer can increase the nuclease resistance and enhance the binding affinity. Studies have shown that the 3’ inverted thymidine cap can stabilize the RNA aptamer for anticoagulant factor IXa in human plasma for at least 5 hours.
Fig. 1 Chemical modification strategies for nucleic acid aptamers.1
3’ Inverted Thymidine Modified Aptamer Development in Creative Biolabs
In ongoing or completed clinical trials, 3'-end capping with inverted thymidine has become a common strategy for aptamers in disease treatment. Our 3' inverted thymidine modified aptamer strategy is rough as follows: the synthesis of aptamers requires a modified CPG, which has the 5'-hydroxyl group of the first nucleoside attached, and then chain lengthening in a standard 3 '→ 5' manner.
Many tools and techniques can be used to improve the stability of aptamers. Understanding stability requirements and determining the best solution to improve stability is a key part of the project design process. The required stability and potential modifications must be carefully considered. As an expert in the field of life science research for more than 10 years, Creative Biolabs has accumulated a lot of project experience and provided creative consulting aptamer discovery and development services.
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We are managed by scientists and are committed to helping other scientists answer research questions through collaborative interaction.
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We are committed to finding the best way to maintain the selectivity and function of aptamers while minimizing the cost and time of aptamer production.
This 3’ inverted thymidine modification for aptamer is available as part of a custom oligonucleotide configuration. Please contact us to speak with a customer service representative.
Reference
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Niederlender, Solène, Jean-Jacques Fontaine, and Grégory Karadjian. "Potential applications of aptamers in veterinary science." Veterinary Research 52.1 (2021): 1-20.
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Questions & Answer
A: The 3' end capping with inverted thymidine has also been a common strategy among aptamers for diseases therapy. Research suggested that 3' inverted thymidine modification could increase the stability and resistance of aptamers to 3' exonuclease in human serum.
A: Synthesis of 3' inverted thymidine modified aptamers needed modified CPG with the 5' hydroxyl of the first nucleoside attached, followed by chain elongation in standard 3'→5' fashion.
A: The stability of selected aptamer that is modified with 3' biotin or 3' inverted thymidine is increased. The 3' biotin and 3' inverted thymidine modified aptamer is strongly resistant to nuclease attack in serum compared to the unmodified aptamer. But the 3' inverted thymidine modification shows higher stability than the 3' biotin modification.
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