One issue that has delayed the revolution is the difficulty associated with the identification of aptamers that bind to a target analyte. For antibodies, the identification process has been well developed and is relatively routine. For aptamers, the reliance on polymerase chain reaction (PCR) based amplifica- tion of very small concentrations of short target DNA molecules can easily lead to artifacts. In addition, without effective counter measures, the immobilization of the analyte onto resin for selection purposes can easily lead to the identification of aptamers for components of the resin, rather than the ana- lyte. It’s been my experience that many published aptamers exhibit significant binding to various resins, and very little to the analyte of interest.
Aptamers have many appealing qualities, including the ability to refold into an active conformation and synthesis with cheap methods in comparison to antibodies (nucleic acids are cheaper and easier to make than proteins). However, a major drawback of aptamers is their low affinity. You've probably noticed that publications involving biosensor development using aptamers focus on just a few targets (e.g., thrombin). These are the few aptamers that have a sufficient binding affinity to be analytically useful. Until someone improves aptamer design methods comparable to produce aptamers with affinities on the order of antibodies (sub-micromolar K_D values), antibodies with be the preferred capture molecule of choice.
That is true that some targets proved to be difficult for selection of aptamers with high affinity. I am not sure that "design methods" [as I understand this term] is the real problem. Based on some recent results, "chemistry" may be a limitation when DNA or RNA aptamers are selected. Several groups have addressed this issue and developed new chemistries for that purpose.
I would cite in no specific order:
Sullenger's group at DUKE, using 2'-F, 2'-OMe and 2'-OH nucleosides
AM Biotech and Gorenstein's at UT Houston, using X-aptamer platform and dithioates
Somalogics - Larry Gold's company - using Somamers [modified nucleosides as well]
TagCyx - Ichiro Hirao's group at Riken, Yokohama - using non-natural bases
Those groups developed aptamers with affinity in the nM or even pM against 100's or even 1000's of targets alltogether.
Here are a few references:
Xianbin Yang et al., 2011, Expert Opin. Drug Discov., 6(1) 75-87
Gold et al., 2012, Cold Spring Harb. Perspect Biol, 4:a003582
Gold L, et al. (2010) PLoS ONE 5(12): e15004. doi:10.1371/journal.pone.0015004
Kimoto, et al. (2013) Nature Biotechnology, online publication 7 April 2013, doi:10.1038/nbt.2556
Tan et al. (2013), dx.doi.org/10.1021/cr300468w | Chem. Rev. 2013, 113, 2842−2862
Ray et al. (2013), Nucl Acid Therapeutics, online publication DOI: 10.1089/nat.2013.0439
Here is another paper describing more aptamer selection successes and addressing the "support/resin" non-specific binding that is a real concern that has to be addressed when selection experiments/strategy are designed.
Aptamers were first described in 1990, but monoclonal antibodies have been used in clinical situations approximately in 1980 . therefore we can not compare them in this regard.
What I can say quickly is that there has been a scientific meeting organized in Italy in October 2013 [2 months ago]. 177 scientists attended the meeting. That indicates a very strong interest.
The program can be found at: http://www.aptamernaples2013.it/home.asp?pgn=9
That will give you a pretty good idea about the field.
Aptamers are used and/or developed in the following areas:
THERAPEUTICS/DRUGS - for instance REGADO - phase III or NOXXON - phase I and II
DIAGNOSTICS - main reference: SOMALOGICS
BIOSENSORS - many papers, too long for this post... google "aptamer + biosensor"
RESEARCH - see in the aptamer naples 2013 program for many exemple
FOOD SAFETY - see paper from NeoVentures above [Penner 2012].
Some people predict a market for aptamers at 2 billion dollars by 2018. I see that as quite optimistic though. However, the business is growing.
Personally, being an oligo chemist, I wish and hope that aptamers will progressively displace monoclonal antibodies but I think it will be a long way.
The success of the SOMALOGICS platform is already claiming some success and this is an excellent point - see http://www.somalogic.com/Technology.aspx
A company like Neoventures could also make a step into Food safety analysis with their product - see http://neoventures.ca/products/mycotoxin-testing/
After that, time will tell us how long it will take.
In my opinion, key to success of aptamer is the ability to deliver on the promise that "Good Aptamer lead can be delivered within 3-6 weeks and optimized aptamer can be obtained after an additional 6 weeks". If THAT can become true, aptamer technology will have a serious advantage. And critical to that is for selection companies to have EXCELLENT LIBRARIES to start selection with.
Unfortunately, there are only a few high-affinity aptamers characterized properly and published. If you ask for examples, you nearly always end up with a thrombin aptamer as shown in the presentation attached above.