High throughput nucleic acid sequencing by expansion
First Claim
1. A method for sequencing a target nucleic acid, comprising:
- a) providing a daughter strand produced by a template-directed synthesis, the daughter strand comprising a plurality of subunits coupled in a sequence corresponding to a contiguous nucleotide sequence of all or a portion of the target nucleic acid, wherein the daughter strand is formed from a plurality of oligomer or monomer substrate constructs, wherein the individual subunits of the daughter strand comprise a tether, at least one probe or nucleobase residue, and at least one selectively cleavable bond, and wherein the tether, upon cleavage of the at least one selectively cleavable bond, permits lengthening of the subunits of the daughter strand;
b) cleaving the at least one secletively caeavable bond to yield an Xpandomer of a length longer than the plurality of the subunits of daughter strand, the Xpandomer comprising the tethers and reporter elements for parsing genetic information in a sequence corresponding to the contiguous nucleotide sequence of all or a portion of the target nucleic acid; and
c) detecting the reporter elements of the Xpandomer.
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Abstract
Nucleic acid sequencing methods and related products are disclosed. Methods for sequencing a target nucleic acid comprise providing a daughter strand produced by a template-directed synthesis, the daughter strand comprising a plurality of subunits coupled in a sequence corresponding to a contiguous nucleotide sequence of all or a portion of the target nucleic acid, wherein the individual subunits comprise a tether, at least one probe or nucleobase residue, and at least one selectively cleavable bond. The selectively cleavable bond(s) is/are cleaved to yield an Xpandomer of a length longer than the plurality of the subunits of the daughter strand, the Xpandomer comprising the tethers and reporter elements for parsing genetic information in a sequence corresponding to the contiguous nucleotide sequence of all or a portion of the target nucleic acid. Reporter elements of the Xpandomer are then detected. Corresponding products, including Xpandomers and oligomeric and monomeric substrate constructs are also disclosed.
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Citations
40 Claims
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1. A method for sequencing a target nucleic acid, comprising:
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a) providing a daughter strand produced by a template-directed synthesis, the daughter strand comprising a plurality of subunits coupled in a sequence corresponding to a contiguous nucleotide sequence of all or a portion of the target nucleic acid, wherein the daughter strand is formed from a plurality of oligomer or monomer substrate constructs, wherein the individual subunits of the daughter strand comprise a tether, at least one probe or nucleobase residue, and at least one selectively cleavable bond, and wherein the tether, upon cleavage of the at least one selectively cleavable bond, permits lengthening of the subunits of the daughter strand; b) cleaving the at least one secletively caeavable bond to yield an Xpandomer of a length longer than the plurality of the subunits of daughter strand, the Xpandomer comprising the tethers and reporter elements for parsing genetic information in a sequence corresponding to the contiguous nucleotide sequence of all or a portion of the target nucleic acid; and c) detecting the reporter elements of the Xpandomer. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40)
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Specification