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Abstract

Peptide nucleic acids (Proc Nat Acad Sci USA) are DNA
mimics consisting of the four common bases as in DNA
on a pseudopeptide backbone that makes them extremely
stable in biological fluids. Antisense PNA can be targeted
to mRNA in the cytoplasm in a complementary base
pairing manner. In order to achieve efficient mRNA based
targeting, endosomal release or direct uptake of
Proc Nat Acad Sci USA into the cytosol is mandatory. However,
relatively poor internalization of these agents is reported
for most cells.
1 Several reports suggested cell penetrating
peptide (CPP) based delivery systems for PNA delivery
into cells.
2 Unfortunately, endosomal capture seems to
be a major challenge in these approaches restricting the
ability of PNA to bind with mRNA. Recent studies have
explored the use of cholesterol-siRNA conjugates to
enhance cellular import.
3 In order to attain efficient PNA
internalization into cells, we synthesized two different
sequences of cholesterol coupled antisense PNA and
evaluated their uptake efficacy in comparison to a PNA-CPP conjugate previously reported by our group.