Out Of The Lab
Craig A. Kasper, Au.D.
Columbia University Technology: Crossreactive Sensor Arrays
Based on DNA Receptors
Drs. Milan N. Stojanovic and Donald W. Landry from Columbia
University's Department of Medicine have developed a novel array system for the
parallel processing of molecular recognition events via arrays of
oligonucleotide-based sensors. The binding domains of these sensors are based
on three-way nucleic acid junctions that form at the intersection of three
double helixes. The double-helical stems are analogous to antibody framework
regions that ensure reliable folding, regardless of variations in or around the
binding domain formed by the three-way junction. The sensors are organized into
cross-reactive arrays to yield characteristic fingerprints for samples
containing hydrophobic molecules.
The principles of this technology draw on the highly
cross-reactive design of the mammalian olfactory system which contains
approximately one thousand unique receptors. Odorants are characterized by a
pattern of massively parallel responses that yield fingerprints that are
characteristic of a specific odorant. In the technology developed by Drs.
Stojanovic and Landry, analytical samples are similarly matched through their
characteristic fingerprints to available standards; incremental structural
variations achieve differential cross-reactivity. A reporting domain is
introduced by the specific substitution of a single phosphodiester group with a
phosphothio, followed by selective functionalization with a fluorophore.
Introduction of a fluorophore into the hydrophobic cavity of the junction
yields a molecular sensor based on the internal displacement of the fluorophore
by a guest molecule.
This sensor array approach can be used to characterize
hydrophobic ligands and to fingerprint complex biologic mixtures. Whereas a
given sensor may weakly discriminate various hydrophobic ligands, an array of
related sensors can achieve considerable specificity. It is anticipated this
technology will have research, drug development and clinical applications.
Some advantages of this technology, as detailed by Drs.
Stojanovic and Landry include:
Offers incremental variations of structure to achieve
differential cross-reactivity, currently a limiting feature - electronic nose
Up to several thousand receptors with similar yet distinctive
characteristics can be organized into cross-reactive arrays
Unique reporter system that utilizes a fluorophore placed in the
hydrophobic cavity of the three-way nucleic acid junction - provides immediate
Preparative scale synthesis of sensors can provide standardized
Applications of this technology include:
Highly sensitive tool for analysis of and distinguishing
characteristics of individual ligands with considerable specificity based on
Offers powerful fingerprinting approach for analysis of complex
mixtures of hydrophobic molecules - permits unambiguous identification of
Provides capability to systematically construct a series of
incrementally varied fluorescent oligonucleotide receptors
Research-based applications in next-generation drug screening
and analog design
Potential clinical applications - e.g. 'mix and measure' urine
assay for diagnosis of gross errors in steroid genesis and similar size
To date, a United States Utility patent has been filed. A PCT
patent application has also been filed. The technology is available for
licensing or sponsored research support. For further information, please
contact Jerry Kokoshka, Ph.D., Tel: 212-305-8884 email: email@example.com or
Shai Gilad Tel: 212-305-5059 email: firstname.lastname@example.org.