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US 2026/0265288 A1Published application
Silicon containing modified nucleotide analogs
AssigneeSingular Genomics Systems, Inc.
InventorsRonald GRAHAM, Zachary TERRANOVA
Life of this patent
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Abstract
Disclosed herein, inter alia, are silicon containing cleavable linkers and compounds for use in nucleic acid sequencing.
Claims20
A method of sequencing a nucleic template acid in a cell or tissue comprising:
- (i) contacting a nucleic acid template hybridized to a primer with a plurality of nucleotide analogues, wherein the nucleic acid template is in the cell or tissue;
- (ii) extending the primer with a polymerase by incorporating a nucleotide analogue having the formula:
- wherein
- B is a divalent nucleobase;
- R1 is a monophosphate moiety, polyphosphate moiety, or nucleic acid moiety;
- R2 and R3 are independently hydrogen, halogen, —CCl3, —CBr3, —CF3, —CI3, —CHCl2, —CHBr2, —CHF2, —CHI2, —CH2Cl, —CH2Br, —CH2F, —CH2I, —CN, —OH, —NH2, —COOH, —CONH2, —NO2, —SH, —SO3H, —SO4H, —SO2NH2, —NHNH2, —ONH2, —NHC(O)NHNH2, —NHC(O)NH2, —NHSO2H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCCl3, —OCF3, —OCBr3, —OCI3, —OCHCl2, —OCHBr2, —OCHI2, —OCHF2, —OCH2Cl, —OCH2Br, —OCH2I, —OCH2F, —N3, —SF5, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, polymerase-compatible cleavable moiety, or an —O-polymerase-compatible cleavable moiety;
- R4 is a fluorescent dye moiety;
- and
- L100 is a divalent linker comprising
- wherein
- R5 and R6 are independently hydrogen, —CN, —OH, —NH2, —COOH, —CONH2, —NO2, —SO3H, —SO4H, —SO2NH2, —NHNH2, —ONH2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
- and
- R7, R8, and R9 are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
- and
- (iii) detecting the fluorescent dye moiety, thereby identifying the nucleotide analogue.
12 more elements
A method of sequencing a nucleic acid template in a cell or tissue comprising:
- a) contacting the nucleic acid template hybridized to a primer with a plurality of nucleotide analogues, where the nucleic acid template is in the cell or tissue;
- b) extending the primer with a polymerase by incorporating a nucleotide analogue having the formula:
- wherein
- B is a divalent nucleobase;
- R1 is a monophosphate moiety, polyphosphate moiety, or nucleic acid moiety;
- R2 is hydrogen, halogen, —CCl3, —CBr3, —CF3, —CI3, —CHCl2, —CHBr2, —CHF2, —CHI2, —CH2Cl, —CH2Br, —CH2F, —CH2I, —CN, —OH, —NH2, —COOH, —CONH2, —NO2, —SH, —SO3H, —SO4H, —SO2NH2, —NHNH2, —ONH2, —NHC(O)NHNH2, —NHC(O)NH2, —NHSO2H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCCl3, —OCF3, —OCBr3, —OCI3, —OCHCl2, —OCHBr2, —OCHI2, —OCHF2, —OCH2Cl, —OCH2Br, —OCH2I, —OCH2F, —N3, —SF5, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or a polymerase-compatible cleavable moiety;
- R3 is
- R4 is a fluorescent dye moiety;
- L100 is a divalent linker;
- R5 and R6 are independently hydrogen, —CN, —OH, —NH2, —COOH, —CONH2, —NO2, —SO3H, —SO4H, —SO2NH2, —NHNH2, —ONH2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
- R7, R8, and R9 are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
- and
- R10 is substituted or unsubstituted alkyl;
- and
- c) detecting the fluorescent dye moiety, thereby identifying the nucleotide analogue.
12 more elements
Dependencies are inferred from the claim text.