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.