Antisense molecules and ribozymes capture the imagination with their p
romise of rational drug design and exquisite specificity. However, the
y are far more difficult to produce than was originally anticipated, a
nd their ability to eliminate the function of a single gene has never
been proven. Furthermore, a wide variety of unexpected non-antisense e
ffects have come to light. Although some of these side effects will al
most certainly have clinical value, they make it hard to produce drugs
that act primarily through true antisense mechanisms and complicate t
he use of antisense compounds as research reagents. To minimize unwant
ed non-antisense effects, investigators are searching for antisense co
mpounds and ribozymes whose target sites are particularly vulnerable t
o attack, This is a challenging quest.