Wednesday, April 11, 2012

Aptamers and Potential Drug Therapies

Hi everyone,

I've learned some about aptamers and their characteristically high affinity and selectivity for their target molecules. For a brief overview, aptamers are single stranded DNA or RNA molecules (usually DNA) that can be selected for using SELEX (Systematic Evolution of Ligands by Exponential Enrichment). This process requires no previous knowledge of the DNA library and essentially allows for the selection of DNA molecules that bind to specific target molecules (i.e. certain glycoforms). To fast forward a bit, the implications of this technology is that cancer therapy may one day be able to target only cancerous cells thereby eliminating most of the negative side effects that are attributed to chemotherapy.

Needless to say, I found this type of research not only intriguing on the conceptual level--but also promising to the therapeutic research community. Attached is a paper about some of the research by Dr. Weihong Tan, a professor at the University of Florida, who has studied aptamers and possible drug uses.

In recent years targeted drug delivery has been attempted by drug-conjugate combinations. "However, when multiple functionalities are involved, the fabrication of the conjugates becomes correspondingly complicated and can compromise the efficacy of these drug candidates" (Yang, et. al). Some of the issues that drug delivery encounters are decreased drug toxicity and resistance. The paper describes how aptamer-conjugates can act as the driving force behind the treatment modality of cellular disruption. Cellular disruption is the process of releasing drugs from inside a cell--one way of "out-smarting" drug resistant cells. Tan's research group has developed polymeric aptamer conjugates that show selective cytotoxicity for cancerous cells. The aptamer conjugates decrease their target cell activity by more than 50%. Overall, the aptamer conjugates target certain (cancerous) cells and display cytotoxicity only after they are internalized by the cell (the aptamer-drug conjugate is essentially harmless to normal cells).

Attached is a link to the scientific paper. Engineering Polymeric Aptamers for Selective Cytotoxicity (Yang et. al.)

Here is a video to help illustrate the aptamer selection process termed SELEX. I would imagine this video is the product of nerds with too much free time (...they probably go to Stanford.)