Epoch Biosciences, Inc.

Elitech Holding B.v.

Epoch Pharmaceuticals, Inc.

Elitechgroup, Inc.

Elitechgroup Mdx LLC

Elitechgroup B.v.

Elitech Holdings B.v.

Yale University

Scarr, Noah

Lukhtanov, Eugeny a.

Eugeny Alexander Lukhtanov

Igor V Kutyavin

Rich B Meyer, Jr

Michael W Reed

Alexei V Vorobiev

Noah Scarr

Nicolaas M J Vermeulen

Alexander A Gall

Irina Aleksandrovna Afonina

Robert O Dempcy

Joel Hedgpeth

Howard B Gamper

Evgeniy S Belousov

Yevgeniy S Belousov

Mikhail A Podyminogin

Yung-Chi Cheng

James H Zhou

Balakrishna S Pai

J Ansel Wald

Jinsuk Woo

Viachaslau Bernat

Alexei Vorobiev

Fluorescence quenching nitrodiarylethene analogs are useful in oligonucleotide conjugates and probes. These analogs, whose absorption spectra are substantially blue-shifted relatively to emission spectra of common fluorophores (such as fluorescein), do not need to rely on spectral overlap of quencher absorbance and fluorophore's emission for their quenching abilities. The oligonucleotide-quencher conjugates may be used in detection methods for nucleic acid targets.

Nitrodiarylethenes as fluorescence quenchers for nucleic acid probes

The carborhodamine dyes disclosed herein are novel reagents suitable for automated incorporation of carborhodamine dyes into oligonucleotides that can be used in detection methods for nucleic acid targets. This disclosure provides an efficient and simple process for the preparation of carborhodamine compounds and introduces previously unknown reagents for the automated synthesis of oligonucleotide-carborhodamine conjugates.

Carborhodamine compounds and methods of preparation thereof

Diaryl-azo derivatives are efficient fluorescence quenchers as well as nucleic acid duplex-stabilizing agents and are useful in oligonucleotide conjugates and probes. The oligonucleotide-quencher conjugates may be used in detection methods for nucleic acid targets.

Duplex stabilizing fluorescence quenchers for nucleic acid probes

Methods, primers and probes are provided for the isothermal amplification and detection, without denaturation, of double stranded nucleic acid targets for polymerase strand displacement amplification ('iSDA'). The methods and compositions disclosed are highly specific for nucleic acid targets with high sensitivity, specificity and speed that allow detection of clinical relevant target levels. The methods and compositions can easily be used to amplify or detect nucleic acid targets in biological samples.

Methods for true isothermal strand displacement amplification

The invention provides methods to identify pRNA- and pDNA oligomer affinity pairs. Affinity pairs comprised of nucleic acid oligomers which demonstrate no cross-reactivity ('orthogonal') are designed using software and empirically verified by thermodynamic study and lateral flow testing. The design software uses a semi-random algorithm to build such sequences of nucleic acid oligomers based on user-input parameters for affinity strength and orthogonal stringency. These pairs can be applied for use in multi-analyte solid support and lateral flow diagnostic tests.

Method of producing oligomer affinity pairs

Artificial nucleosides including 2-methyl-nucleobase-substituted butane-1,3-diol nucleosides are disclosed. Four different stereoisomers of such nucleosides are possible. Oligonucleotides made up of the artificial nucleosides form homoduplexes of greater stability than DNA duplexes and have a reduced ability to hybridize to DNA or RNA.

Artificial nucleic acids

3-alkynyl inosine analogs and their uses as universal bases are provided. The inosine analogues can be incorporated into nucleic acid primers and probes. They do not significantly destabilize nucleic acid duplexes. As a result, the novel nucleic acid primers and probes incorporating the inosine analogues can be used in a variety of methods. The analogs function unexpectedly well as universal bases. Not only do they stabilize duplexes substantially more than hypoxanthine opposite A, C, T, and G but they are also recognized in primers by polymerases, allowing efficient amplification.

Functionalized 3-alkynyl pyrazolopyrimidine analogues as universal bases and methods of use

Minor groove binder phosphoramidites having the formula M-L-PA, wherein M is a minor groove binder comprising a protected heteroaromatic amine, L is a linker, and PA is a phosphoramidite group, have been synthesized. Preferred methods of synthesis include synthesizing a minor groove binder intermediate containing a transiently protected hydroxyl group, protecting heteroaromatic amines of the corresponding minor groove binder intermediate as carbamate intermediates, reacting the carbamate intermediate to remove the transient protecting group to yield carbamate-protected minor groove binder agent as an intermediate with a free hydroxyl group, and converting the intermediate with a free hydroxyl group to the desired minor groove binder phosphoramidite. These minor groove binder phosphoramidites are useful in the preparation of oligonucleotide conjugates, particularly those for use as probes and primers. In preferred methods, an oligonucleotide sequence is synthesized using nucleoside phosphoramidites and the minor groove binder phosphoramidite is incorporated into the oligonucleotide sequence to form a protected oligonucleotide-minor groove binder conjugate. Then, deprotection produces the oligonucleotide-minor groove binder.

Minor groove binder phosphoramidites and methods of use

3-alkynyl inosine analogs and their uses as universal bases are provided. The inosine analogs can be incorporated into nucleic acid primers and probes. They do not significantly destabilize nucleic acid duplexes. As a result, the novel nucleic acid primers and probes incorporating the inosine analogs can be used in a variety of methods. The analogs function unexpectedly well as universal bases. Not only do they stabilize duplexes substantially more than hypoxanthine opposite A, C, T, and G but they are also recognized in primers by polymerases, allowing efficient amplification.

Growing community of inventors

Bothell, WA, United States of America

Eugeny Alexander Lukhtanov