Lasergen, Inc.

Baylor College of Medicine

Merck + Co., Inc.

Other

William Marsh Rice University

Redvault Biosciences, LP

Agilent Technologies, Inc.

The Wellcome Trust Limited As Trustee for the Wellcome Trust

Michael L Metzker

Weidong Wu

Brian P Stupi

Vladislav A Litosh

Megan N Hersh

Sidney E Morris

David Hertzog

Hong Li

Richard A Gibbs

Carter Kittrell

John W Hess

Charles T Caskey

Holly A Hammond

David L Gerhold

Yusuke Nakagawa

Robert F Curl

Michael S Phillips

Patricia Hey

Yoshihiko Kawaguchi

Graham B I Scott

Roger D Cox

Tony R Merriman

John A Todd

Rebecca C J Twells

Christopher August Weier

Xiaomei Liu

Chang Bai

C Thomas Caskey

Konstantin Petrukhin

Claes Wadelius

Rebecca Cj Twells

Brian Philip Stupi

Provided herein are methods and compositions for the detection of target nucleic acids using target reporter constructs (TRCs) which comprise target sequences complementary to the target nucleic acid. Further provided are methods of replicating the TRCs using rolling circle replication and/or rolling circle amplification to produce replicated TRCs which can be detected using probe sequences within the replicated TRCs.

Target reporter constructs and uses thereof

The present invention relates generally to 3'-OH unblocked nucleotides and nucleosides labeled and unlabeled with 5-methoxy-substituted nitrobenzyl-based photocleavable terminating groups for use in methods and systems related to DNA and RNA sequencing and analysis. These compounds may be used as reversible terminators as they exhibit fast nucleotide incorporation kinetics, single-base termination, high nucleotide selectivity, and rapid terminating group cleavage that results in a naturally occurring nucleotide.

3'-OH unblocked, fast photocleavable terminating nucleotides and methods for nucleic acid sequencing

The present invention relates generally to labeled and unlabled cleavable terminating groups and methods for DNA sequencing and other types of DNA analysis. More particularly, the invention relates in part to nucleotides and nucleosides with chemically cleavable, photocleavable, enzymatically cleavable, or non-photocleavable groups and methods for their use in DNA sequencing and its application in biomedical research.

Nucleotides and nucleosides and methods for their use in DNA sequencing

Provided are novel nucleotides, nucleoside, and their derivatives described herein, that can be used in DNA sequencing technology and other types of DNA analysis. In one embodiment, the nucleotide or nucleoside with an unprotected 3'-OH group is derivatized at the nucleobase to include a fluorescent dye attached via a linker to a photocleavable terminating group. The photocleavable-fluorescent group is designed to terminate DNA synthesis as well as be cleaved so that DNA oligomers can be sequenced efficiently in a parallel format. The design of such rapidly cleavable fluorescent groups on nucleotides and nucleosides can enhance the speed and accuracy of sequencing of large oligomers of DNA in parallel, to allow rapid whole genome sequencing, and the identification of polymorphisms and other valuable genetic information, as well as allowing further manipulation and analysis of nucleic acid molecules in their native state following cleavage of the fluorescent group.

Photocleavable labeled nucleotides and nucleosides and methods for their use in DNA sequencing

The present invention relates generally to 3'-OH unblocked, labeled and unlabeled nucleotides and nucleosides with 5-methoxy-substituted nitrobenzyl-based photocleavable terminating groups for use in methods and systems related to DNA and RNA sequencing and analysis. These compounds, which may be represented by the following formulas: wherein the variables are defined herein, may be used as reversible terminators as they exhibit fast nucleotide incorporation kinetics, single-base termination, high nucleotide selectivity, and rapid terminating group cleavage that results in a naturally occurring nucleotide.

The present invention relates generally to labeled and unlabeled cleavable terminating groups and methods for DNA sequencing and other types of DNA analysis. More particularly, the invention relates in part to nucleotides and nucleosides with chemically cleavable, photocleavable, enzymatically cleavable, or non-photocleavable groups and methods for their use in DNA sequencing and its application in biomedical research.

3'OH-unblocked, nucleotides and nucleosides base modified with labels and photocleavable, terminating groups and methods for their use in DNA sequencing

Provided are novel nucleotides, nucleoside, and their derivatives described herein, that can be used in DNA sequencing technology and other types of DNA analysis. In one embodiment, the nucleotide or nucleoside with an unprotected 3'-OH group is derivatized at the nucleobase to include a fluorescent dye attached via a linker to a non-cleavable terminating group. The non-cleavable-fluorescent group is designed to terminate DNA synthesis so that DNA oligomers can be sequenced efficiently in a parallel format. These reagents and methods will lead to more accurate identification of polymorphisms and other valuable genetic information.

3'-OH unblocked nucleotides and nucleosides base modified with non-cleavable, terminating groups and methods for their use in DNA sequencing

The present invention provides a technology called Pulse-Multiline Excitation or PME. This technology provides a novel approach to fluorescence detection with application for high-throughput identification of informative SNPs, which could lead to more accurate diagnosis of inherited disease, better prognosis of risk susceptibilities, or identification of sporadic mutations. The PME technology has two main advantages that significantly increase fluorescence sensitivity: (1) optimal excitation of all fluorophores in the genomic assay and (2) 'color-blind' detection, which collects considerably more light than standard wavelength resolved detection. Successful implementation of the PME technology will have broad application for routine usage in clinical diagnostics, forensics, and general sequencing methodologies and will have the capability, flexibility, and portability of targeted sequence variation assays for a large majority of the population.

Pulsed-multiline excitation for color-blind fluorescence detection

Growing community of inventors

Houston, TX, United States of America

Michael L Metzker