Peptide conjugated, inosine-substituted antisense oligomer compound and method

摘要

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.

主权项

1. An oligomer-peptide conjugate comprising an arginine-rich peptide conjugated to a substantially uncharged antisense oligonucleotide compound, the oligonucleotide compound comprising a base sequence complementary to a string of contiguous cytosine bases, and wherein the base sequence comprises at least one inosine base and no more than two contiguous guanine bases.