Why Aren’t Aptamers Mainstream?

Aptamers are not considered a conventional technique. Aptamer selection technology was developed about a quarter of a century ago. In the beginning, aptamers were immediately thought to be a revolutionary start into solving many problems associated with the diagnostics and the therapy of diseases. However, multiple attempts to use aptamers in practice generally have been less efficient than what was expected initially, although some attempts were successful. There are problems impeding the widespread application of aptamers in diagnostics and therapy. The rapid breakdown of aptamers, especially RNA aptamers, by nucleases in biological media is a serious problem that puts limits on their practical application. The problem is that oligonucleotides can break down in just minutes, which is too short for most practical applications of an aptamer.

Aptamers also don’t stay in human bloodstream for too long because of our filtration systems. Human kidneys are able to remove substances with molecular weights smaller than most aptamers(15-50 nucleotides). Another setback with aptamers is that aptamer generation, in most cases, requires the availability of purified target molecules. Protein target molecules are expressed in cell cultures and purified by affine chromatography. These procedures are time and labor-consuming, thus delaying the production of corresponding aptamers.

Additionally, regardless of an aptamers high specificity, aptamers that recognize particular targets can also bind to molecules with a similar structure. Aptamer cross-reactivity can be an obstacle to their therapeutic application because of the possible side effects caused by aptamer interaction with other proteins; however, this problem can be avoided by introducing a SELEX negative selection step with structurally similar molecules.

Generation of aptamers seems to be a rather simple protocol, but in reality it is a time-

and labor-consuming process. The selected aptamers sometimes turns out not to have the best affinity and specificity due to a sub-optimal SELEX procedure. The SELEX process does not even guarantee that an adequate aptamer is created. There are many steps where things could go wrong. This includes problems like, degradation, contamination, accidentally selecting for the wrong target. Then after all that, you have to sequence your pool to what potential candidates their are for aptamers and then get those synthesized. Then, they must be tested on their target to see if they can even be called successful aptamers.

Even after 20 years of the creation of the SELEX process to select aptamers, only one aptamer is approved for use in therapeutics(Macugen). We still have a ways to go before aptamers can be utilized to their full potential. Several different solutions have been proposed and even put to use for the problems mentioned above but they still have not been enough to get the aptamer revolution started. As we get closer to developing quicker and more standardized protocols that are able to develop aptamers that avoid the mentioned current constraints, aptamers should start to become more mainstream.

 

 

REFERENCE

Lakhin, A. V., Tarantul, V. Z., & Gening, L. V. (2013). Aptamers: problems, solutions and prospects. Acta naturae, 5(4), 34-43.

 

About us:

Faith Murphy, Pre- Med focus on genetics.

Matthew Ponce, Mechanical Engineering.

Alexander Chui, Computer Science.