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Why Have Aptamers Not Been More Successful in Therapeutics?

    I love the confidence of those responding. Basically the winning category was that aptamers work great, they just have not been tried in enough applications. 

    In my opinion, we should have provided a fifth option in this poll, All of the above… 

    Successful monoclonal antibody based treatments are all based on the capacity of the antibody to induce an immune response once it has bound to its target. This is the fundamental principle behind Mab treatments. We do not expect aptamers to induce an immune response. This means that this entire scope of treatment applications are potentially not appropriate for aptamers. I think that aptamer applications in therapy are more likely to be in areas where a suppression of an immune response is desired, such as auto-immune diseases. Aptamer binding to the target in these cases has the potential to reduce antibody binding and thus reduce the severity of the response. We have explored the potential of aptamers for treatment of Alzheimer’s disease as a means of reducing chronic inflammation in the brain. 

    The next two options, aptamers clear to rapidly  and aptamers do not bind well enough are related to each other. If aptamers bind to their target with sufficient strength then they will clear less rapidly. The rapid clearance of aptamers through the renal system is a tremendous potential advantage for aptamers in terms of favourable pharmacodynamics. Aptamers that bind aspecifically to other components in serum especially serum albumin may also have longer retention times. 

    Very definitely there have been insufficient clinical trials with aptamers in comparison with antibodies. The failure rate of clinical treatment trials is very high, and the failure rate of antibodies is in line with this. I think that the key to success for aptamers in therapeutic trials is appropriate positioning of the application. There is no point in developing aptamers to compete with antibodies in this area. 

    The majority of our work with partners in therapeutics is the use of aptamers as vectors for the targeted delivery of drugs. We have the capacity to select aptamers for transmembrane receptors such that the selected aptamers either will induce endocytosis and thus can be used to carry other drugs (especially RNA drugs) into cells, or aptamers that will bind to transmembrane receptors and not induce endocytosis. This latter application is of interest for prophylactic applications of aptamers to prevent virus entry into cells, or to down regulate existing transmembrane receptor activity. 

    If you are interested in discussing your aptamer based therapeutic application with us, please register on our website for a free consultation and we look forward to talking with you. 

     

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