Development of universal antidotes to control aptamer activity.

dc.contributor.author

Oney, S

dc.contributor.author

Lam, RTS

dc.contributor.author

Bompiani, KM

dc.contributor.author

Blake, CM

dc.contributor.author

Quick, G

dc.contributor.author

Heidel, JD

dc.contributor.author

Liu, JYC

dc.contributor.author

Mack, BC

dc.contributor.author

Davis, ME

dc.contributor.author

Leong, KW

dc.contributor.author

Sullenger, BA

dc.coverage.spatial

United States

dc.date.accessioned

2013-04-29T17:49:24Z

dc.date.issued

2009-10

dc.description.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.

dc.identifier

http://www.ncbi.nlm.nih.gov/pubmed/19801990

dc.identifier

nm.1990

dc.identifier.eissn

1546-170X

dc.identifier.uri

https://hdl.handle.net/10161/6931

dc.language

eng

dc.publisher

Springer Science and Business Media LLC

dc.relation.ispartof

Nat Med

dc.relation.isversionof

10.1038/nm.1990

dc.subject

Anticoagulants

dc.subject

Antidotes

dc.subject

Aptamers, Nucleotide

dc.subject

Drug Delivery Systems

dc.subject

Drug Design

dc.subject

Factor IX

dc.subject

Factor Xa Inhibitors

dc.subject

Humans

dc.subject

Nucleic Acid Conformation

dc.subject

Oligonucleotides

dc.subject

Protamines

dc.subject

Time Factors

dc.title

Development of universal antidotes to control aptamer activity.

dc.type

Journal article

pubs.author-url

http://www.ncbi.nlm.nih.gov/pubmed/19801990

pubs.begin-page

1224

pubs.end-page

1228

pubs.issue

10

pubs.organisational-group

Basic Science Departments

pubs.organisational-group

Biomedical Engineering

pubs.organisational-group

Clinical Science Departments

pubs.organisational-group

Duke

pubs.organisational-group

Duke Cancer Institute

pubs.organisational-group

Institutes and Centers

pubs.organisational-group

Molecular Genetics and Microbiology

pubs.organisational-group

Pharmacology & Cancer Biology

pubs.organisational-group

Pratt School of Engineering

pubs.organisational-group

School of Medicine

pubs.organisational-group

Surgery

pubs.organisational-group

Surgery, Surgical Sciences

pubs.publication-status

Published

pubs.volume

15

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