Unintended "side-effects" of gene therapy

Mon, 13 Mar 1995 13:26:38 -0500

On March 7 Mike Lieber wrote questioning whether geneticists have discussed 2
issues: pleiotropy and polygenic effects in terms of gene therapy. The short
answer is yes though this has come predominantly from geneticists and not
ethicists as the issues are extremely technical. Polygenic effects are those
where a particular sequence of genes are needed to work together to produce
a particular protein outcome. Intuitively it would seem that getting these
genes out of order would disturb the normal flow and produce an untoward
effect. So far this has not been the case as the sequential order of genes is
constantly changing by recombination so this experiment has been carried out
by nature since the beginning. Gene therapy studies to date have shown that
imprecise gene targeting makes some difference in terms of quantity of
product but not quality.
Pleiotropic effects are really quite similar in that the gene in question may
operate in more than one pathway. This is also not altered by imprecise
targeting. This discussion was very early on in studies for gene therapy but
has tapered off in recent years as these effects seem to make little
Lawrence G. Leichtman, M.D.