Peptide conjugated, inosine-substituted antisense oligomer compound and method
First Claim
1. A method for enhancing the cellular uptake of a substantially uncharged antisense oligonucleotide compound, wherein the compound comprises a base sequence complementary to a string of at least four contiguous cytosine bases, the base sequence comprising one or more inosine bases and no more than three contiguous guanine bases, the method comprising forming a conjugate of the compound and an arginine-rich peptide.
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Abstract
A therapeutic oligomer-peptide conjugate, and methods of using the conjugate are disclosed. The conjugate includes (a) a substantially uncharged oligonucleotide analog compound having a base sequence that includes a string of bases that are complementary to four or more contiguous cytosine bases in a target nucleic acid region to which the compound is intended to bind, and (b) conjugated to the compound, an arginine-rich peptide effective to enhance the uptake of the compound into target cells. The string of bases in the compound includes at least one inosine base positioned in the string so as to limit the number of contiguous guanine bases in said string to three or fewer. The conjugate has greater cellular uptake than the compound alone, by virtue of the arginine-rich peptide, and substantially greater antisense activity greater activity than the conjugate in the absence of inosine for guanine substitutions.
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Citations
33 Claims
- 1. A method for enhancing the cellular uptake of a substantially uncharged antisense oligonucleotide compound, wherein the compound comprises a base sequence complementary to a string of at least four contiguous cytosine bases, the base sequence comprising one or more inosine bases and no more than three contiguous guanine bases, the method comprising forming a conjugate of the compound and an arginine-rich peptide.
- 11. A method for preparing a conjugate of a substantially uncharged antisense oligonucleotide compound and an arginine-rich peptide, wherein the compound comprises a base sequence complementary to a string of at least four contiguous cytosine bases, the method comprising including at least one inosine bases in the base sequence such that the base sequence comprises no more than three contiguous guanine bases.
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20. An oligomer-peptide conjugate comprising:
- (a) an arginine-rich peptide conjugated to a substantially uncharged antisense oligonucleotide compound, the compound comprising a base sequence complementary to a string of at least four contiguous cytosine bases and wherein the base sequence comprises at least one inosine bases and no more than three contiguous guanine bases.
- View Dependent Claims (21, 22, 23, 24, 25, 26, 27, 28, 31, 33)
Specification