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Apr 18, 2013
 |  BC Innovations  |  Tools & Techniques

Expanding the aptamer alphabet

Researchers at the RIKEN Center for Life Science Technologies and TagCyx Biotechnologies have used an expanded genetic alphabet containing unnatural nucleotides to generate DNA aptamers that have 100-fold higher binding affinity for a target protein than counterparts created using only natural nucleotides.1 The group plans to develop the aptamers for diagnostic applications before exploring therapeutic applications.

Nucleic acid aptamers consist of single strands of DNA or RNA and are usually generated via in vitro approaches such as SELEX (systematic evolution of ligands by exponential enrichment), in which aptamers from a library undergo iterative rounds of selection to enrich for aptamers with the highest affinity for a particular target.

However, generating molecules with the desired level of functionality usually is less efficient for nucleic acid aptamers than for peptides and proteins. The reason is that a four-nucleotide genetic alphabet limits chemical and structural diversity, according to Ichiro Hirao, leader of the synthetic molecular biology team at the RIKEN Center for Life Science Technologies and founder, president and CEO of TagCyx.

Conventional peptides and proteins are generated using a 20-amino-acid alphabet.

For more than a decade, Hirao and colleagues in Japan have been developing base pairs of unnatural nucleotides that could be used to expand the standard genetic alphabet and yield oligonucleotides with new properties and functionality. These nucleotide pairs are designed to be compatible with DNA/RNA replication and transcription but only form base pairs with one another and not with any of the four natural nucleotides.

Hirao and colleagues...

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