Gene Therapy for Cancer Treatment - Biotechnology and Your Health: Pharmaceutical Applications - page 104

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and some antisense molecules are now being studied in human
cancer patients. However, the only FDA-approved antisense drug is
fomiversin (Vitravene ® ), which is used to treat cytomegalovirus
infection of the eye. (Cytomegalovirus [CMV] is a common DNA
virus related to the viruses that cause chicken pox, mononucleosis,
and fever blisters. CMV does not usually make people sick, but it
can hide out in the body, and if the immune system is weakened, it
can cause illness and damage to the retina.) Fomiversin is injected
directly into the eye.
Discovered in the 1980s, ribozymes are RNA molecules with a
very distinct hammerhead structure. They function as enzymes and
directly cut RNA. Synthetic ribozymes targeted to specific messen-
ger RNAs have been used in many laboratory studies with cells.
Efforts to develop ribozyme treatments targeted to specific cancer
genes and for other uses have not succeeded in clinical trials, partly
because the structure of the ribozyme that is needed to allow it to
work as an enzyme was destroyed when it was injected.
Over the last few years, research has suggested that antisense
doesn't work simply by interfering with the ability of the protein-
making machinery to read the messenger RNA. Instead, it must
actually set up the message to be destroyed. Laboratory experiments
with cells indicated that in some cases, the single-stranded antisense
was less effective in preventing the production of the targeted
protein than a double-stranded RNA made up of the antisense and
sense sequences. Double-stranded interfering RNA has become a
very useful laboratory tool for studying the function of a protein.
This is because the message for the protein targeted by the interfer-
ing RNA is destroyed and the protein production is stopped, or at
least severely curtailed. If you knock out the protein and see what
goes wrong, you can understand more about what the protein does.
However, as with vector-based gene therapy, fooling Mother Nature
is not so easy. First, if double-stranded RNA is delivered to cells at
too high a concentration, it is not specific and may damage other