The mathematics of SELEX against complex targets

Vant-Hull, Barry; Payano-Baez, Antonio; Davis, Robert H.; Gold, Larry

doi:10.1006/jmbi.1998.1727

Cited by 79 publications

(68 citation statements)

References 38 publications

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“…Moreover, some targets may not be purified or may be included with other target species in a mixture, so it can be difficult to obtain a desired single target component of interest from a mixture with multiple target species. It is also known that aptamers can be isolated against multiple target components using the SELEX process ( [17], [23], [24], [30]). We refer to this process as multiple target SELEX.…”

Section: Mathematical Models For Selexmentioning

confidence: 99%

“…The authors in [30] suggested the method of subpooling nucleic acid species with similar affinities against each target. This subpooling strategy allows them to identify, simultaneously, a mixture of high affinity nucleic acids against all target species.…”

Section: Mathematical Models For Selexmentioning

confidence: 99%

“…In this thesis, we reexamine the method in [30] and analyze the multiple target SELEX process. It is assumed all species are present in sufficient amounts so the law of large numbers can be applied to use average values for species concentrations.…”

Section: Outline Of the Thesismentioning

confidence: 99%

“…The primary goal is to charac-terize the limiting values of the nucleic acid concentrations in terms of the initial and limiting experiment parameters when selection occurs. We note here that, in a laboratory, the SELEX process is usually taken through fewer than 25 rounds (see [30], page 580). Even though we do not restrict the use of a large number of rounds to reach the limiting states, we believe that our mathematical approach will provide a good understanding of the multiple-target SELEX process for experimentalists.…”

Section: Outline Of the Thesismentioning

confidence: 99%

“…The SELEX process typically begins with a random library of up to 10 15 DNA or RNA molecules ( [30]). Once target-NA bound products are obtained and partitioned from unbound NA molecules, the bound NA molecules are eluted and amplified using a method such as PCR.…”

Section: Introductionmentioning

confidence: 99%

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A Mathematical Analysis of Multiple-Target Selex

et al. 2010

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Section: Mathematical Models For Selexmentioning

confidence: 99%

Section: Mathematical Models For Selexmentioning

confidence: 99%

Section: Outline Of the Thesismentioning

confidence: 99%

Section: Outline Of the Thesismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Mathematical Analysis of Multiple-Target Selex

et al. 2010

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Theoretical Principles of In Vitro Selection Using Combinatorial Nucleic Acid Libraries

Vant-Hull

Gold

Zichi

2000

CP Nucleic Acid Chemistry

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A new paradigm for drug discovery and biological research has developed from technologies that integrate combinatorial chemistry with rounds of selection and amplification, a technique called in vitro selection or systematic evolution of ligands by exponential enrichment (SELEX). This overview unit discusses nucleic acid libraries that can be used, affinity probability distributions, an equilibrium model for SELEX, and optimal conditions including concentrations and signal-to-noise ratios.

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Properties of Therapeutic Aptamers

Cload

McCauley

Keefe

et al. 2006

The Aptamer Handbook

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Since the invention of the SELEX process and the isolation of the first protein-specific aptamers, parallels to the functional properties of monoclonal antibodies have been drawn. While antibodies have demonstrated utility in a number of settings, their development as therapeutic agents has been long and difficult and it is only in the last 5 years that the field has matured to the stage where one can point to a number of unqualified clinical successes. In many respects, the opportunities for aptamers as therapeutics continue to parallel those for antibodies although the technical challenges have been somewhat different. 2004 was a milestone year for the field with the US Food and Drug Administration (FDA) approval of pegaptanib (Macugenä). In this chapter, we review the properties of aptamers as druglike molecules, highlighting their functional capabilities as target-specific binding agents and our current understanding of how aptamers behave in vivo with respect to distribution, metabolism, and tolerability. The antibody experience provides important lessons for the development of aptamer therapeutics and points the way for future applications which will particularly favor progress with aptamers. Aptamer TargetsThe collected experience of both academic and industry research suggests that aptamers are capable of binding to targets from virtually any protein class (Sullenger and Gilboa, 2002). While early efforts focused largely on nucleic acid-binding targets (e.g.

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The mathematics of SELEX against complex targets

Cited by 79 publications

References 38 publications

A Mathematical Analysis of Multiple-Target Selex

A Mathematical Analysis of Multiple-Target Selex

Theoretical Principles of In Vitro Selection Using Combinatorial Nucleic Acid Libraries

Properties of Therapeutic Aptamers

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