Send in the Modifications
War movies are full of it. Bullets whizzing past the infantry. Supplies dwindling to the last scrap of shoe leather. The enemy advancing ever closer. Morale falling faster than the apple hitting Sir Isaac Newton’s head. Suddenly, a burst of brilliant light emerges from beyond the hills heralding the arrival of reinforcements. The battered infantry is reinvigorated to make that final push on the enemy’s line and claims victory.
Outside of such Hollywood moments, the arrival of reinforcements actually happens routinely and even in the most unlikely of places. For example, a test tube. Though an unlikely location, scientists at SomaLogic saw the benefits upon the arrival of reinforcements.
At the core of SomaLogic’s technology are SOMAmer® reagents. These reagents are “evolved” to bind a protein and are composed of varying amounts of four nucleic acid bases, one of which is modified with “protein-like” sidechains. These modified bases in turn enable the SOMAmer to tightly bind its target protein, even in a complicated mix of many different proteins.
This effect raises an interesting question: If modifying one of the four bases used to create SOMAmers yields such great protein binders, what happens when reinforcements are added (e.g., what if two of the four bases are modified)? To answer this question, SomaLogic scientists modified a second base, and found that the number of very strong binding SOMAmers significantly increased (as did the number of different binding sites on the target protein) (Gawande et al., 2017). They also found that they could make shorter SOMAmers with no apparent loss of binding capabilities.
These reinforcing modifications and enhanced traits expand the number of proteins that can be targeted by SOMAmers (and, by extension, the reach of the SOMAscan assay into the proteome). They also increase the already broad range of uses for SOMAmer reagents. For example, the use of SOMAmers with two modifications makes it easier to find pairs for sandwich assays (e.g., an assay in which one SOMAmer captures the protein and second SOMAmer detects the captured protein, making a “sandwich” around the protein). With the small size and great stability, the two modifications may make SOMAmers worthy therapeutic candidates or great tools for other applications, such as drug delivery. Clearly, the arrival of these modification reinforcements only strengthens the power of the SOMAmer technology.
Gawande, B. N., Rohloff, J. C., Carter, J. D., von Carlowitz, I., Zhang, C., Schneider, D. J., & Janjic, N. (2017). Selection of DNA aptamers with two modified bases. Proc Natl Acad Sci U S A. doi:10.1073/pnas.1615475114