Classical gene augmentation therapy

Classical gene augmentation therapy is not suitable for
disorders that are due to the production of an abnormal
protein that has a harmful effect because of its altered
function. This applies to autosomal dominant disorders where
the mutation has a dominant negative effect, producing a
protein with a new and detrimental function, as in Huntington
disease. Genetic manipulation in this type of disorder requires
targeted correction of the gene mutation or the inhibition of
production of the abnormal protein product. Several
methodologies involving DNA or RNA modification are
currently being investigated.
Other approaches to gene therapy include the increased
expression of protein isoforms not normally expressed in the
affected tissue, or the upregulation of other interacting genes
whose products may ameliorate the disease process. In
Duchenne muscular dystrophy, for example, it is possible that
upregulation of a protein called utrophin, that is related to
dystrophin, may have some beneficial effect in slowing the
progression of muscle damage.