In order to protect them against enzymatic attack of serum in the antisense
strategy, oligodeoxyribonucleotides can be protected on their 3'-side by t
he sequence d(GCGAAGC) which spontaneously forms a hairpin which is known f
or its extraordinary stability with regard to thermal denaturation or nucle
ase degradation (I. Hirao, G. Kawai, S. Yoshizawa, Y. Nishimura, Y. Ishido,
K. Watanabe and K. Miura, Nucleic Acids Res. 22, 576-582 (1994)). By contr
ast, the hairpin does not prevent hybridization of the 5'-stem part of the
oligonucleotide to a target DNA strand. As soon as this pairing occurs, the
stability of the hairpin is disrupted. Its opening rate, followed by its p
airing if possible, is of the same order than that of hybridization of the
stem part.