Modified DNA aptamers: Two is better than one
In a study published online on March 6, 2017 in the Proceedings of the National Academy of Sciences (PNAS), SomaLogic scientists report on the generation and characterization of a new class of SOMAmer that contains two different types of modified nucleotides. Current SOMAmer® reagents contain deoxyuridine (dU) bases with protein-like modifications at the 5-position, which increases the chemical diversity of SOMAmer libraries and expands the number and type of protein targets that can be bound. Now, for the first time, researchers have created new SOMAmer libraries that contain an additional base: a 5-position modified deoxycytosine (dC).
The researchers synthesized a total of 18 different SOMAmer libraries that contained zero, one or both types of modified bases. To test the libraries, they selected new SOMAmers against the known human therapeutic target protein, proprotein convertase subtilisin/kexin type 9 (PCSK9), a critical protein in heart health. They found that the SOMAmers with the best binding to PCSK9 contained both types of modified bases. Similar results were observed with another target protein, prostate-specific membrane antigen (PSMA), a predictor for progression and prognosis of prostate cancer.
SomaLogic researchers are now incorporating these new SOMAmer reagents in ongoing studies across a wide range of biomedical science, from basic research to therapeutic applications.
Reference: Gawande et al. (2017) Selection of DNA aptamers with two modified bases Proceedings of the National Academy of Sciences, published ahead of print March 6, 2017, doi:10.1073/pnas.1615475114