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Article: Closed-loop control of cellular functions using combinatory drugs guided by a stochastic search algorithm

TitleClosed-loop control of cellular functions using combinatory drugs guided by a stochastic search algorithm
Authors
KeywordsFeedback control
Drug resistance
Drug cocktail
Combinatory drug therapy
Viral infection
Issue Date2008
Citation
Proceedings of the National Academy of Sciences of the United States of America, 2008, v. 105, n. 13, p. 5105-5110 How to Cite?
AbstractA mixture of drugs is often more effective than using a single effector. However, it is extremely challenging to identify potent drug combinations by trial and error because of the large number of possible combinations and the inherent complexity of the underlying biological network. With a closed-loop optimization modality, we experimentally demonstrate effective searching for potent drug combinations for controlling cellular functions through a large parametric space. Only tens of iterations out of one hundred thousand possible trials were needed to determine a potent combination of drugs for inhibiting vesicular stomatitis virus infection of NIH 3T3 fibroblasts. In addition, the drug combination reduced the required dosage by ≈10-fold compared with individual drugs. In another example, a potent mixture was identified in thirty iterations out of a possible million combinations of six cytokines that regulate the activity of nuclear factor kappa B in 293T cells. The closed-loop optimization approach possesses the potential of being an effective approach for manipulating a wide class of biological systems. © 2008 by The National Academy of Sciences of the USA.
Persistent Identifierhttp://hdl.handle.net/10722/285623
ISSN
2023 Impact Factor: 9.4
2023 SCImago Journal Rankings: 3.737
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorPak, Kin Wong-
dc.contributor.authorYu, Fuqu-
dc.contributor.authorShahangian, Arash-
dc.contributor.authorCheng, Genhong-
dc.contributor.authorSun, Ren-
dc.contributor.authorHo, Chih Ming-
dc.date.accessioned2020-08-18T04:56:13Z-
dc.date.available2020-08-18T04:56:13Z-
dc.date.issued2008-
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America, 2008, v. 105, n. 13, p. 5105-5110-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/285623-
dc.description.abstractA mixture of drugs is often more effective than using a single effector. However, it is extremely challenging to identify potent drug combinations by trial and error because of the large number of possible combinations and the inherent complexity of the underlying biological network. With a closed-loop optimization modality, we experimentally demonstrate effective searching for potent drug combinations for controlling cellular functions through a large parametric space. Only tens of iterations out of one hundred thousand possible trials were needed to determine a potent combination of drugs for inhibiting vesicular stomatitis virus infection of NIH 3T3 fibroblasts. In addition, the drug combination reduced the required dosage by ≈10-fold compared with individual drugs. In another example, a potent mixture was identified in thirty iterations out of a possible million combinations of six cytokines that regulate the activity of nuclear factor kappa B in 293T cells. The closed-loop optimization approach possesses the potential of being an effective approach for manipulating a wide class of biological systems. © 2008 by The National Academy of Sciences of the USA.-
dc.languageeng-
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America-
dc.subjectFeedback control-
dc.subjectDrug resistance-
dc.subjectDrug cocktail-
dc.subjectCombinatory drug therapy-
dc.subjectViral infection-
dc.titleClosed-loop control of cellular functions using combinatory drugs guided by a stochastic search algorithm-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1073/pnas.0800823105-
dc.identifier.pmid18356295-
dc.identifier.pmcidPMC2278193-
dc.identifier.scopuseid_2-s2.0-42449099889-
dc.identifier.volume105-
dc.identifier.issue13-
dc.identifier.spage5105-
dc.identifier.epage5110-
dc.identifier.eissn1091-6490-
dc.identifier.isiWOS:000254723700028-
dc.identifier.issnl0027-8424-

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