Methods for production of arrays with modified oligonucleotide and polynucleotide compositions
First Claim
1. An array comprising:
- (A) a support surface; and
(B) a plurality of modified oligonucleotide compositions, each composition comprising a plurality of oligonucleotides stably associated with a distinct area of the support surface, wherein the oligonucleotides of each composition are characterized by;
(1) independently having a length of from about 20 to about 300 nucleotides;
(2) having internucleotide linkages selected from the group consisting of 2′
-O-alkyl, 2′
-O-alkyl-n(O-alkyl), combinations thereof;
(3) having a binding affinity to a complementary sequence greater than the corresponding binding affinity of a non-modified oligonucleotide having the same sequence; and
(4) having a pH stability of at least one hour at 37°
C. at a pH in a range of about 0.5 to 6.
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Abstract
The present invention provides methods for producing arrays having associated modified nucleic acid structures, e.g. acid stable and/or end-blocked nucleic acids such as 2′-O—R oligonucleotides. In one embodiment, arrays produced using the methods of the invention exhibit an increased binding affinity with complementary nucleic acids, and in particular with complementary RNA. In another embodiment, the associated nucleic acids of the array produced using the methods of the invention exhibit substantial acid resistance, allowing the arrays to be treated with low pH solutions. In another embodiment, the modified associated nucleic acids of the array produced using the methods of the invention exhibit substantial resistance to nuclease degradation.
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Citations
12 Claims
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1. An array comprising:
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(A) a support surface; and
(B) a plurality of modified oligonucleotide compositions, each composition comprising a plurality of oligonucleotides stably associated with a distinct area of the support surface, wherein the oligonucleotides of each composition are characterized by;
(1) independently having a length of from about 20 to about 300 nucleotides;
(2) having internucleotide linkages selected from the group consisting of 2′
-O-alkyl, 2′
-O-alkyl-n(O-alkyl), combinations thereof;
(3) having a binding affinity to a complementary sequence greater than the corresponding binding affinity of a non-modified oligonucleotide having the same sequence; and
(4) having a pH stability of at least one hour at 37°
C. at a pH in a range of about 0.5 to 6. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)
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Specification