Team:TU Eindhoven/Achievements/Future Outlook/RCA

Future Outlook Rolling Circle Amplification on Cells

As was mentioned in the introduction of this part of our project there are many possible reasons why it is useful to attach DNA to the outside of cell membranes. The obvious example would be aptamers which display similar recognition and diversity as antibodies. They provide an advantage in the form of the ability to bind to toxins to which a normal immune response is not triggered. [1] This means we could use these aptamers when combined to signaling proteins to help bacteria sense their environment even better and more controllable than before. A system consisting of one generic signal-relay protein and a set of clickable aptamers could be a great start for many functional cells with easily changeable ligands.

It is also possible to create DNA with protein like functionalities in order to create so called DNA enzymes. These enzymes have been created to catalyze a diverse range of reactions, including RNA cleavage, DNA cleavage, RNA ligation, DNA ligation, deglycosylation, and other enzymatic activities as peroxidases. [2] Since DNA can be made to function as an enzyme we envision a system in which a DNA based enzyme could work as a pre-processor before a potentially harmful metabolite enters the bacteria. The DNA enzyme coating surrounding the cell can break down toxins so that the cell can utilize them. The advantage of using DNA over proteins clicked to the cell is the same as for aptamers, DNA has proven to be much more stable than proteins.

Lastly, DNA also shows promising capabilities as a designer material. Since DNA can be made to form self-assembling structures whose function and form can be determined in advance it is possible to design many interesting shapes. [3] The field of DNA engineering is just starting out, but already many applications have been developed to make use of DNA’s unique ability to form links to complementary strands. [4] Also it has been shown that DNA can be used to form hydrogels, which could potentially mean that DNA can be used to coat cells in an antifouling coating which has therapeutic use. [5]

Bibliography

[1] Navani, N., & Li, Y. (2006). Nucleic acid aptamers and enzymes as sensors.Current Opinion in Chemical Biology,10(3), 272-281.

[2] Liu, J., Cao, Z., & Lu, Y. (2009). Functional Nucleic Acid Sensors. Chemical Reviews,109(5), 1948-1998.

[3] Seeman, N. C. (2003). DNA in a material world. Nature, 421(6921), 427-431.

[4] Cadnano. (n.d.). cadnano. Retrieved October 14, 2014, from http://cadnano.org/.

[5] Lee, J. B., Wu, M., Luo, D., Long, R., Chen, L., Rice, E. J., et al. (2012). A mechanical metamaterial made from a DNA hydrogel. Nature Nanotechnology,7(12), 816-820.