Abstract: Embodiments of the present disclosure relate to nucleotides labeled with photoswitchable compounds. Also provided herein are methods and kits of using these labeled nucleotides for sequencing applications.
Abstract: This disclosure provides methods for bisulfite-free identification in a nucleic acid sequence of the locations of 5-methylcytosine, 5-hydroxymethylcytosine, 5-carboxylcytosine and 5-formylcytosine.
Type:
Grant
Filed:
March 7, 2022
Date of Patent:
April 16, 2024
Assignee:
Ludwig Institute for Cancer Research, LTD
Abstract: Methods and kits for sequencing a nucleic acid molecule are provided, which include utilizing four different compounds that are respectively derivatives of nucleotides A, (T/U), C and G, wherein the hydroxyl at the 3?-position of sugar of each of the four compounds is protected by a reversible protecting group. Each of the four compounds comprises a first linker, a second linker, and a terminal molecular label binding to or reactive to a receptor in a detectable group comprising a luminescence-activating molecule and the receptor, the luminescence-activating molecule capable of causing emission of fluorescence in the presence of a suitable substrate. The second linkers in the four compounds are different, and can be cleaved at different conditions.
Abstract: Compounds useful as fluorescent or colored dyes are disclosed. In some embodiments, the compounds have the following structure (I): or a stereoisomer, tautomer or salt thereof, wherein R1, R2, R3, R4, R5, L1, L2, L3, L4, M1, M2, m, and n are as defined herein. Methods associated with preparation and use of such compounds is also provided.
Abstract: The present disclosure provides labeling reagents for labeling substrates such as nucleotides, proteins, antibodies, lipids, and cells. The labeling reagents provided herein may comprise fluorescent labels and semi-rigid linkers. Methods for nucleic acid sequencing using materials comprising such labeling reagents are also provided here.
Type:
Grant
Filed:
March 17, 2022
Date of Patent:
April 2, 2024
Assignee:
Ultima Genomics, Inc.
Inventors:
Linda G. Lee, Gilad Almogy, Steven Menchen
Abstract: Embodiments may include a nucleic acid molecule system. The system may include a nucleic acid polymerase attached to a tether compound. The polymerase may be configured to elongate a nascent strand. The system may also include a nucleotide attached to a label compound. The label compound may include a moiety. The system may further include a transistor in electrical communication with a power supply. The polymer may be attached to the transistor. In addition, the system may include a meter device configured to measure an electrical characteristic of the transistor from the moiety after the label compound is cleaved from the nucleotide by the nucleic acid polymerase.
Abstract: Provided are methods for labeling target molecules, such as nucleic acids, with fluorescent dye compounds having the formula One method embodiment includes contacting reactive group Z of the fluorescent dye compound with the target molecule such that reactive group Z reacts with the target molecule to form a covalent bond between the group and the target molecule. Another method embodiment includes contacting a fluorescent dye compound that further includes a first member of a binding pair, with a target molecule that includes a second member of the binding pair. Also provided are target molecules labeled with the fluorescent dye compounds.
Abstract: 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.
Abstract: The present invention provides, among other things, methods of quantitating mRNA capping efficiency, particularly mRNA synthesized in vitro. In some embodiments, methods according to the present invention comprise providing an mRNA sample containing capped and uncapped mRNA, providing a cap specific binding substance under conditions that permit the formation of a complex between the cap specific binding substance and the capped mRNA, and quantitatively determining the amount of the complex as compared to a control, thereby quantifying mRNA capping efficiency.
Type:
Grant
Filed:
May 19, 2021
Date of Patent:
March 5, 2024
Assignee:
TRANSLATE BIO, INC.
Inventors:
Michael Heartlein, Frank DeRosa, Anusha Dias
Abstract: Activity-based probes that can be used to selectively identify and characterize enzymes that are involved in different phases of xenobiotic metabolism in a host and its microbiota population(s) are described. The activity-based probes described specifically label only their target active enzymes involved in xenobiotic metabolism and therefore provide a measurement of true protein functional activity rather than transcript or protein abundance. The activity-based probes also provide multimodal profiling of these active enzymes. Methods for preparing the activity based probes and exemplary methods for their use also are disclosed.
Type:
Grant
Filed:
April 26, 2022
Date of Patent:
February 6, 2024
Assignee:
Battelle Memorial Institute
Inventors:
Aaron T. Wright, Susan Ramos-Hunter, Christopher Whidbey
Abstract: Provided for herein is a method for detecting the presence of a nucleic acid target molecule in a biological sample. In certain aspects, the method comprises contacting a test sample that comprises (i) a biological sample comprising a nucleic acid target molecule and (ii) an osmylated single-stranded oligonucleotide probe comprising at least one pyrimidine residue covalently bonded to a substituted or unsubstituted Osmium tetroxide (OsO4)-2,2?-bypyridine group (OsBp group).
Abstract: The present application relates to exocyclic amine-substituted coumarin derivatives and their uses as fluorescent labels. These compounds may be used as fluorescent labels for nucleotides in nucleic acid sequencing applications.
Type:
Grant
Filed:
July 1, 2022
Date of Patent:
January 30, 2024
Assignee:
Illumina Cambridge Limited
Inventors:
Nikolai Nikolaevich Romanov, Carole Anastasi, Patrick McCauley
Abstract: Labeled nucleotide analogs comprising at least one avidin protein, at least one dye-labeled compound, and at least one nucleotide compound are provided. The analogs are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The analogs are detectable with high sensitivity at desirable wavelengths. They contain structural components that modulate the interactions of the analogs with DNA polymerase, thus decreasing photodamage and improving the kinetic and other properties of the analogs in sequencing reactions. Also provided are nucleotide and dye-labeled compounds of the subject analogs, as well as intermediates useful in the preparation of the compounds and analogs. Compositions comprising the compounds, methods of synthesis of the intermediates, compounds, and analogs, and mutant DNA polymerases are also provided.
Type:
Grant
Filed:
December 20, 2021
Date of Patent:
January 30, 2024
Assignee:
Pacific Biosciences of California, Inc.
Inventors:
Lubomir Sebo, Honey Osuna, Stephen Yue, Yuri Lapin
Abstract: Methods and systems and related compositions for separating through a solid matrix a mixture comprising a nucleic acid in a concentration of 1 ?M or less, together with a target compound having a water solubility equal to or greater than 0.001 g per 100 mL, which can be used for managing fluid flow, biochemical reactions and purification of the nucleic acid or other target analytes. The method comprises contacting the solid matrix with a target compound removing agent having a water solubility equal to or less than 0.05 g per 100 mL at 25° C. at 1 atm pressure with water having a solubility in the removing agent of less than 10 g per 100 mL at 25° C. at 1 atm pressure, the contacting performed to remove the target compound from the solid matrix.
Type:
Grant
Filed:
December 22, 2020
Date of Patent:
January 9, 2024
Assignee:
CALIFORNIA INSTITUTE OF TECHNOLOGY
Inventors:
Rustem F. Ismagilov, Erik Jue, Daan Witters
Abstract: The present application relates to secondary amine-substituted coumarin compounds and their uses as fluorescent labels. The compounds may be used as fluorescent labels for nucleotides in nucleic acid sequencing applications.
Type:
Grant
Filed:
July 1, 2022
Date of Patent:
January 2, 2024
Assignee:
Illumina Cambridge Limited
Inventors:
Nikolai Nikolaevich Romanov, Patrick McCauley, Carole Anastasi, Xiaolin Wu, Niall Hynes