Selection and amplification of aptamers - artistic representation with Ds in yellow and the aptamer complex in green
DNA aptamers are strands of DNA oligonucleotides that have the ability to bind to target molecules, such as proteins, and could be used as diagnostic tools and therapeutic agents. However, conventional DNA aptamers consisting of natural or modified natural nucleotides often lack the desired binding affinity and specificity to target proteins.
Dr Hirao and his team now working at the Division of Structural and Synthetic Biology of the RIKEN Center for Life Science Technologies in Yokohama have developed a new method to greatly increase aptamer affinity and specificity. They generated DNA aptamers through evolutionary engineering using an oligonucleotide library containing adenine, guanine, thymine, cytosine and the highly hydrophobic unnatural base, Ds.
They show that their aptamers containing Ds bases at only a few positions bind to two human target proteins with an affinity that is 100 times higher than aptamers containing only natural bases.
These results indicate the potential of genetic alphabet expansion as a powerful tool for creating highly functional nucleic acids.
They are presented in the journal Nature Biotechnology, doi:10.1038/nbt.2556