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Development of universal antidotes to control aptamer activity

Oney, Sabah and Lam, Ruby T. S. and Bompiani, Kristin M. and Blake, Charlene M. and Quick, George and Heidel, Jeremy D. and Liu, Joanna Yi-Ching and Mack, Brendan C. and Davis, Mark E. and Leong, Kam W. and Sullenger, Bruce A. (2009) Development of universal antidotes to control aptamer activity. Nature Medicine, 15 (10). pp. 1224-1229. ISSN 1078-8956. doi:10.1038/nm.1990. https://resolver.caltech.edu/CaltechAUTHORS:20091102-140636691

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1038/nm.1990 DOIUNSPECIFIED
http://www.nature.com/nm/journal/v15/n10/abs/nm.1990.htmlPublisherUNSPECIFIED
ORCID:
AuthorORCID
Davis, Mark E.0000-0001-8294-1477
Additional Information:© 2009 Nature Publishing Group. Received 28 July 2008; accepted 13 May 2009; published online 4 October 2009. Author contributions: S.O. designed and performed research, analyzed data and wrote the manuscript; R.T.S.L designed and performed research and analyzed data; K.M.B. performed research; C.M.B. performed research and analyzed data; G.Q. performed research; J.D.H. designed and performed research, provided useful reagents, analyzed data and provided useful discussions; J.Y.-C.L. performed research; B.C.M. performed research; M.E.D. provided useful reagents and discussions; K.W.L. provided useful reagents and discussions; B.A.S. suggested the universal antidote idea, designed and coordinated research, analyzed data and wrote the manuscript. Methods and any associated references are available in the online version of the paper at http://www.nature.com/naturemedicine/. Note: Supplementary information is available on the Nature Medicine website. We thank S.M. Nimjee and J. Layzer for helpful discussions and Calando Pharmaceuticals for providing the CDP and CDP-Im polymers. This work was supported by a grant from the US National Institutes of Health (HL065222 to B.A.S.), a predoctoral fellowship from the American Heart Association (0615443U to S.O.) and a grant from the US National Cancer Institute (CA 119347 to M.E.D).
Funders:
Funding AgencyGrant Number
NIHHL065222
American Heart Association0615443U
U.S. National Cancer InstituteCA 119347
Issue or Number:10
DOI:10.1038/nm.1990
Record Number:CaltechAUTHORS:20091102-140636691
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20091102-140636691
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:16544
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:03 Nov 2009 22:33
Last Modified:08 Nov 2021 23:27

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