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- Title
Development of universal antidotes to control aptamer activity.
- Authors
Oney, Sabah; Lam, Ruby T. S.; Bompiani, Kristin M.; Blake, Charlene M.; Quick, George; Heidel, Jeremy D.; Liu, Joanna Yi-Ching; Mack, Brendan C.; Davis, Mark E.; Leong, Kam W.; Sullenger, Bruce A.
- Abstract
With an ever increasing number of people taking numerous medications, the need to safely administer drugs and limit unintended side effects has never been greater. Antidote control remains the most direct means to counteract acute side effects of drugs, but, unfortunately, it has been challenging and cost prohibitive to generate antidotes for most therapeutic agents. Here we describe the development of a set of antidote molecules that are capable of counteracting the effects of an entire class of therapeutic agents based upon aptamers. These universal antidotes exploit the fact that, when systemically administered, aptamers are the only free extracellular oligonucleotides found in circulation. We show that protein- and polymer-based molecules that capture oligonucleotides can reverse the activity of several aptamers in vitro and counteract aptamer activity in vivo. The availability of universal antidotes to control the activity of any aptamer suggests that aptamers may be a particularly safe class of therapeutics.
- Subjects
ANTIDOTES; DRUG side effects; OLIGONUCLEOTIDES; DRUG administration; NUCLEIC acids; BLOOD circulation; THERAPEUTICS
- Publication
Nature Medicine, 2009, Vol 15, Issue 10, p1224
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/nm.1990